Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
Knowledge is treasure of a wise man. The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help ones reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journalsNo manuscriptsNo authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Reviews
Year : 2008 | Month : December | Volume : 2 | Issue : 6 | Page : 1226 - 1233

Multidisciplinary Approach and Pivotal Role of Pathologist in Diagnosis of Breast Cancer: Technological Advances: An Updated Review for Breast Health Care experts

PATRA S.B

MD (Path &Micro),FIC Path.Ex-Prof&HeadMedicalCollegeBaroda.Consultant Pathologist Ex-Visiting ProfessorKesar SAL Medical College,Ahmedabad(GUJARAT) Prof of Pathology, MTH/MCOMS,POKHARA(NEPAL)

Correspondence Address :
1-Dhanushya society-1.New Sama road Baroda:390008,Ph:91-265-2789165,91-09998723704,e.mail:sbpatra2002@yahoo.com

Abstract

Clinical and pathological diagnosis of breast carcinoma is advancing at the same pace as the global increase in its incidence, morbidity and mortality. Research scientists (bio molecular, pathologists, clinicians and geneticists) are working on war footing for prevention, cure and treatment of breast cancer. In near future, breast cancer diagnosis may advance inexplicably.
The pathology report serves not only as a hard copy for clinicians on which various treatment modalities are based , but also as a teaching module for educated cancer patients. The pathologist, who plays a very critical and pivotal role, hardly meets the patient in most institutional set ups. In unlimited resource centers, his/her role is very critical, because patients themselves can challenge clinicians and sue the pathologist.
The scientific document based on observation can be finite, but the pathologist has to go beyond the finite observation, because many technical and clinical variations and limitations have to be taken into consideration. A guarded analytical opinion along with suggestions has to be given for the patient.
Diagnosis of breast carcinoma has leaped rapidly from FNAC to DNA with many intermediaries in between. In some institutes, the best possible cost effective diagnosis is given, whereas in others, molecular studies are done to provide the diagnosis which influences the therapeutic and prognostic outlook.

Keywords

Diagnosis of breast carcinoma, Multidisciplinary approach, global pathologists

In 2003, BHGI (Breast Health Global Initiative) convened a panel of breast cancer experts to develop a consensus recommendation for clinical and pathological diagnosis in limited resource countries (1) and guidelines were updated (2).The International group met again in 2005 at Bethesda, Maryland. The panel, consisting of 12 countries including India, discussed the recent advances in clinical and pathological diagnosis of breast cancer and charted down the guidelines as per WHO recommendations (3), (4).
It provides a logical, systematic frame work for building Breast Cancer Diagnosis in the best possible way, to be adopted as per the infrastructure and available resources, adhering to the guidelines and implementing it according to the recommendation by BHGI.
There were 4 stratification schemes (Table/Fig 1).
1. Basic-Methods absolutely required for diagnosis.
2. Limited-Large improvement on the basic level.
3. Enhanced-Small improvement on limited level.
4. Maximal-Where unlimited facilities are available for diagnosis and treatment.

Issues related to clinical and pathological diagnosis
Every health care institution (in small / metropolitan city) should follow these guidelines for better heath care and better clinico-pathological coordination and for fewer constraints to authorities, health providers and patients .This would focus & unfold many unknown environmental ,familial & genetic basis of breast breast cancer.

a)Goal of Diagnosis: To determine whether the tumor is benign/malignant, noninvasive/invasive, permitting timely and appropriate care.

b) Definitions:

Clinical diagnosis
- Involves clinical examinations supplemented by mammography, CT with or without FNAC and/or core needle biopsy.
Pathological diagnosis – Involves using various investigative tools.

C) Simplicity of the process: Tissue retrieval should be adequate, as the patient faces barriers in approaching various clinical experts.

d) Quality of the process: The pathology report should provide all details of pathological findings, including molecular studies if available, to meet the requirements of clinicians. As far as possible, they should discuss with the pathologist, any query not befitting their clinical findings and investigations.

e) Correlation of findings: Pathology report need to be correlated with clinical findings for better results.
The "triple test" is suggested
1-clinical & imaging +ve biopsy –ve.
2-clinical or imaging +ve biopsy negative.
3-A repeat biopsy necessary.
f)Importance of the system: For the implementation of guidelines of BHGI in limited resource countries, in addition to resources needed to perform and interpret the biopsy the following are also essential: provision for tissue labeling, transportation, documentation of the pathology report, communication of the results with health care personnel and patient follow up.

DIAGNOSTIC PROCEDURES

1. Clinical

*History taking like family history, AIDS, malaria etc.
*Clinical breast examination-(CBE), Nipple discharge, retraction, metastasis (5), (6).
*Serum alkaline phosphatase for skeletal metastasis.
*Diagnostic mammography for synchronous or metachronus tumor in contra lateral breast.
*Diagnostic Ultrasound-------Particularly for an asymptomatic patient and for palpable tumor, for further clinical and pathological investigations.

2. Pathological
From the establishment of initial diagnosis, to determining the stage of malignancy, this carries both prognostic and therapeutic implications.
Basic pathological techniques like FNAC or core needle biopsy are mandatory in limited resource countries .This is done by palpation and/or supplemented by imaging techniques, either in a clinic or operation theatre (7).
Fine Needle Aspiration Cytology (FNAC)
FNAC helps to determine whether the lump is benign or malignant. Problem is encountered with intermediate hyperplastic lesions, where it is difficult to decide, what to do, in such cases if the pathologist’s report and clinical findings are complementary, or if the FNAC is very diagnostic., the clinician can go ahead with palliative or other surgical treatment (8). Provision should be there for a second opinion in regional centers. Multiple samples will enhance the diagnostic accuracy (9).

Core Needle Biopsy
In non-palpable or small tumors, image guided single or multiple core needle (removed by cutting needles) biopsies and automated gun biopsy is recommended after appropriate patient selection (10).
Limitations: Interpretation of certain tumor types like atypical medullary carcinoma and proper tumor grading for intermediate lesions may not be possible (11)

Surgical Biopsy
In patients having large primary tumors,
larger tumor samples may be needed for more
histopathological information.

Record Keeping
Medical Record

-To know p-TMN (Pathological) and c-TMN (Clinical), for regional and/or global statistical comparative data, ethnic group involved (12); hence, can keep data for prevailing pattern.
-To communicate the results to other health care providers.
-Diagnostic protocols may enhance the improvement of prevalent techniques. Insufficient samples documented as False +ve. False-ve, true +ve cases recorded.
-It can be useful for planning resource allocation.

Registries
The medical record provides information for individual patients. The registry provides such information for the populations. So, there should be introduction of local, regional and national registries at limited, enhanced and maximal levels.

Follow Up
In addition to its obvious benefits in terms of continuity of care and support of the patient, it is essential for assessing diagnostic performance. The frequency of insufficient samples should be documented.

Pathology Report
The accurate pathology report starts with the clinician who provides the necessary data The pathology report gives a predictive knowledge, taking into consideration, clinical and bio molecular parameters (13), which also facilitates the patient’s education and respects their autonomy..
-Triple Test is necessary if FNA or Core Biopsy is used (14)
-ER/PR study is recommended if treatment
for Tamoxifen, Aromatase inhibitor or
surgical/ medical ablation is possible.
-HER2/neu based diagnosis and treatment is costly, hence possible only at maximal level set up.

Predictive Value of Pathology Report
Histopathology type, tumor size, lymph node status and tumor grade are absolute requirements for the predictive value at least at the basic level, as it determines the type of therapy.

Role of Pathologist In Multidisciplinary Institutions And Unlimited Resource Centers
There are many challenges for pathologists in multidisciplinary breast cancer diagnosis in institutions with unlimited resources, because of molecular and genetic advances
Steps are suggested where the breast cancer clinical team and the patients can ensure optimal outcome from the pathology report, where the pathologist’s role is very different from limited resource countries (15).The multidisciplinary team consists of :
1-The pathologist.
2-Radiologists, oncosurgeon, oncophysician, oncotherapist, nurse, social worker and physical therapist .

Initial Diagnosis of Breast Cancer
CORE NEEDLE BIOPSY-A good biopsy

gives treatment options like conservative
Surgery or nonadjuvent therapy.
Tumor grading is possible. If the sample is
adequate and if supplemented with ER/PR,
HER2/Neu can outline treatment modalities.
DCIS can be treated by lumpectomy.

FNAC
Either single or multiple only, can give a diagnosis of malignancy under IMAGE GUIDE by quick dip method, and can be later confirmed by PAP. No treatment decisions can be taken at this point.
But flow cytometric studies can be done and other molecular studies can be done, Including cancer genomics and proteomics.

Pathology Report, Patient’s Perceptive.
The pathology report is the patient’s teaching module, as patients in countries with unlimited resources are always concerned, whether there is an ERROR.
The patient may ask for a second opinion in such cases.

Pathology Report as Patient Teaching Module In Unlimited Resource Centers
A Second Opinion

Opinion variation may be very trivial. It may vary from grade-1 to grade-2 due to the observer’s interpretation of nuclear contour, size and tubule formation, which may not affect the treatment much. Hence, the patient has to be informed of such variations by the treating doctor or pathologist.

Hormone Receptor Status
The ER/PR status can not be relied upon due to:
1. Variability in setting norms.11% to 10% staining is considered to be low positive. Some laboratories report it as positive or negative, which is tough to interpret.
2. Technical errors may occur.
3. Two different tissue samples in two labs may give variable results.
4. Sensitivity of the technique used, may give variable results.
Both the pathologist and the clinician should take this into consideration and proceed accordingly. Generally, ER/PR negative cancer and HER2/neu positive cases have a poor survival rate and an early metastasis. The pathologist should put in the report as prognostication for the patient’s perceptive.

Special Cancer Types and Subtleties of Interpretation
As stated earlier, core needle biopsy will not give required information like grade, special cancer types, or even a sampling variation of molecular features. Hence, a pathologist should be very watchful and give only guarded and minimum information in such maximal facility institutions, after thorough discussion with the clinical team.

HER2/Neu status and Breast Cancer
HER2/Neu directed therapy can change cancer prognosis(16). Women with estrogen and progesterone-receptor (ER/PR) negative and HER2-positive disease have a poor prognosis, and should be treated aggressively after the initial diagnosis. This confirms the need for novel treatment strategies for HER2-positive and ER/PR-negative patients, and emphasizes the survival difference in HER2-positive patients depending on their ER and PR status. The pathologist’s role is only to report the molecular findings and give a foot note of the probable prognosis.

Issues on the ER/PR and Her2/Neu Status
Even for a triple negative patient (ER –ve, PR –ve and HER2/neu– ve), there is no molecular based therapy. Pathologists, while reporting, should keep in mind the real negative results, as the test results may vary right from fixation, tissue handling and sampling errors. Only chemotherapy and other adjuvant therapy can be given. But metastatic spread, even with adequate therapy, is affected by a new molecular factor found recently i.e. Fascin, an actin based expression as mentioned below.

Molecular Research.
A pathologist who is a morphologist,
basically looking under simple H&E slides as Dr Juan Rosai has rightly said, “There is a marriage between a morphologist and molecular biologist”[(17]. In his article, he has mentioned the following. “Provided any new technique provides information of prognostic or therapeutic significance beyond that current gold standard, these technologies can be simply viewed as different ways to explore the various levels of complexity within the tree of life: DNA–RNA–protein–cell–tissue–organism, starting with the genotype and ending with the phenotype.
BUT NEW MOLECULAR RESEARCH HAS ITS OWN SINGNIFICANCE MAY UNFOLD CERTAIN INTRICACIES IN CANCER DIAGNOSIS, BIOLOGICAL BEHAVIOR & TREATMENT MODALITIES.
NEW MOLECULAR RESEARCH
Recently the expression of “fascin”, an actin-bundling motility-associated protein, has been found to be responsible for less disease free interval and overall survival in ER and PR negative cases. There was no correlation between fascin expression and HER2 status, or between fascin expression and the pattern of metastases. (Table/Fig 2), (Table/Fig 3). Given fascin’s role in altering cell motility, over expression may contribute to a more aggressive clinical course in ER/PR-negative breast cancers (18).

Oncotype DX™ for predicting risk of breast cancer recurrence
Oncotype DX™ is a novel genetic test designed to accurately predict relapse in women with node-negative and ER-positive breast cancers, who are receiving tamoxifen. This test kit is now commercially available from ‘Genomic Health’.  This is the first genetic test marketed for predicting outcomes of patients with cancer.  Patients with breast cancer may request information about the relevance of Oncotype DX™ for treatment of their disease (19).

One of the first steps in the development of ncotype DX™ was perfecting the reverse transcriptase-polymerase chain reaction (RT-PCR) to detect m-RNA levels in paraffin-embedded (EPE) tumor tissues. This study compared a 48-gene assay from frozen or EPE tissues from the same tumor.  This study also showed that RT-PCR on archival material was concordant with immunohistochemistry assays for estrogen receptor, progesterone receptor and HER2 receptor. 

It would appear from these data, that the test could be clinically useful in reassuring 50% of patients with ER-positive, node-negative and low-risk disease, that they are unlikely to benefit from adjuvant chemotherapy in addition to tamoxifen.  Whether or not patients with intermediate and high-risk breast cancer will benefit from adjuvant chemotherapy in addition to tamoxifen remains to be determined; however, a more accurate determination of the risk of relapse can undoubtedly help patients in their decision making.

The Human Genome Team is taking pathologists and Breast cancer health care experts from the unknown to the known in scientific domain. In future, many things will be revealed .So in countries with unlimited resources, breast cancer diagnosis to a certain extent, is dependent on pathologists who are engaged in routine diagnostic work, but its prognosis, biological behavior and the patient’s future, but is dependent on molecular biologists and geneticists to a larger extent in modern era Such facilities is beyond the reach of patients in many counties.
But wherever such facilities are available for a debatable case, should be utilized. In certain developing countries, it is available in some institutions.

A New Digital Image Histopathology
Pathologists in enhanced & maximal resource centers use ‘A new Digital Image’ microscopy to speed up cancer diagnosis (20). The ultra-rapid virtual scanner gives pathologists a quicker way to break down a biopsy. No pathologist or special lab is needed for the test, just the machine. Situated on top of the microscopes, a 24-megapixel camera captures multiple images. Then the photographs are digitally transmitted immediately over the Internet. “If a patient comes in here at 11 o’clock in the morning, by 3 o’clock in the afternoon, they’ll have gotten a diagnosis,” A new cancer scanner can be used for any type of cancer, the results can be seen worldwide in an instant over the Internet and an opinion can be taken by dynamic telepathology. More than half of the breast cancer patients, who sought a second opinion from a multidisciplinary tumor board, received a change in their recommended treatment plan, which is a boon to heath providers in developing countries.

Nanotechnology and breast cancer diagnosis (21)
Nanotechnology is a function-based technology to measure the softness of the so- called morphologically benign cells. As cancer cells are softer than benign or atypical cells, they can be detected by AFM microscopy, which, by putting a cantilever on the cell membrane, can detect the cell softness in the cells of lesions which appear to be benign. In contrast to structure-based approach in other molecular tests it has a function-based approach. Besides giving out a diagnosis on the functional basis of individual tumor cells, it can even solve many genome-oriented diagnoses, which cannot be solved by existing Genomic technologies. But it is not easily accessible even in technically advanced resource centers
in developing countries Its use in Breast cancer till today is mostly missing malignant cells in effusions by conventional microscopy.

Summary & Concluding remarks
Keep your knowledge abreast, work according to the perview of the institution where you are working, encourage the junior pathologists for modern technological applications, be satisfied with simple H and E stain light microscopy if it is the only available resource and do the best for the patients at large. As far as possible, pathologists in a different set up, from small cities to metropolitan cities, from limited resource centers to expanded resource centers, should try to follow a set of norms in the best possible way, balancing objective technological findings and their analytical power and inner intuition, keeping in mind all variables at all levels, from clinics to laboratory, to dispatch of reports.

Looking into all types of objective tests from FNAC to DNA, many individual breast cancers are similar where clinicians and pathologists may say that they have done their best and that the rest was “beyond science”, until other technical advances like Nanotechnology are available, whose applications promise a brighter future for breast cancer patients.

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