RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE,
KARNATAKA
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidateand address (in block letters) / Dr. BINDU.B.J
D/O B.M. JAGADEESH
2ND MAIN , 6TH CROSS
VIDYANAGAR,
CHITHRADURGA- 577502
2. / Name of the Institution / J.J.M. MEDICAL COLLEGE
DAVANGERE-577004,
KARNATAKA.
3. / Course of Study & Subject / POST-GRADUATE
M.D IN PATHOLOGY
4. / Date of Admission to Course / 3rd JUNE 2011
5. / Title of the topic / “HISTOMORPHOLOGY OF BREAST CARCINOMA AND EVALUATION OF
ESTROGEN AND PROGESTERONE RECEPTORS AND HER2/neu EXPRESSION.”
6. / BRIEF RESUME OF THE INTENDED WORK:
6.1 Need for the study :
Carcinoma of the breast remains one of the leading cancers in women today with an estimated life time risk of 13%.[1]
Morphologic classification of breast carcinomas divide these tumours into a number of subtypes. Aproximately three fourth of mammary carcinoma are invasive ductal or lobular type.Within these,and also among other morphologic categories,tumours display marked heterogeneity in many of their biologic properties.One is the expression of steroid receptors in concert with the oncogene Erb B2/Human epidermal growth factor receptors2( HER2).This has important clinical implications,such as selection of patients for endocrine therapy.[2],3
A large number of studies have correlated the presence or absence of tumour estrogen receptor(ER) or progesterone receptors(PR) with ultimate clinical outcomes.In addition to pathological grade and stage, we set out to evaluate tumour ER/PR status and HER2/ neu overexpression by Immunohistochemistry (IHC) as a prognostic and predictive factors in breast carcinoma. 1
6.2 Review of Literature:
WHO in the year 2003 has classified various malignant epithelial tumours of the breast. 4
Histologic subtype is one of the classical parameters which determine the natural history and outcome in breast carcinoma.Most special subtypes,including tubular,mucinous (colloid) and papillary carcinoma confer a favourable prognosis relative to infiltrating ductal carcinoma NOS.5
Invasive Ductal carcinoma (IDC) is the largest group of malignant mammary tumours,comprising 75% to 80% of mammary carcinomas.The histologic appearance of IDC is heterogenous.Invasive ductal carcinoma,NOS includes tumours that express in part one or more characteristics of the specific types of breast carcinoma,but do not constitute pure examples of the individual tumours. 6
Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer and accounts for 5% to15% of all breast cancer cases.The classical form of ILC is characterized by small relatively uniform neoplastic cells that invade the stroma singly and in a “single-file” pattern resulting in linear strands. 7
Invasive micropapillary carcinoma (IMPCa) of breast is histologically characterized by growth of cohesive tumour cell clusters within prominent clear spaces resembling dilated angiolymphatic vessels. IMPCa with a dominant micropapillary growth pattern account for less than 2% of all invasive breast carcinoma.5
Tubular carcinoma is microscopically composed of small glands or tubules .The cells in tubular carcinoma glands are usually homogeneous in a given lesion. Cystoplasmic tufts/snouts are often present at the luminal cell border. Pure tubular carcinoma constitutes less than 2% of all breast carcinoma.8
A variety of carcinomas in the breast are characterized by production of abundant extracellular and/ or intracellular mucin. Among these are Mucinous carcinoma, Mucinous cystadeno carcinoma, Columnar cell mucinous carcinoma and Signet ring cell carcinoma .4
IMMUNOHISTOCHEMISTRY:
Breast carcinoma is the predominant malignancy where oncologist use predictive markers clinically to select treatment options with steroid receptors having been used for many years .Immuno histochemistry has taken over as the major assay method used for assessing markers. 9
It is recommended that ER and PR assays be considered positive if there are atleast 1% positive tumour nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. 10
Tumours with positive ER results tend to be well differentiated histologically ,to lack tumour necrosis and to have a good nuclear grade. Two favourable histologic variants of carcinoma breast ( i.e., tubular carcinoma and mucinous carcinoma) predominantly have ER. 11
Cancers with positive ER finding respond favourably to hormone or endocrine therapy in approximately 60% of patients. When both receptors are present there is a 70 -75% response rate.11
Well differentiated and moderately differentiated invasive lobular carcinomas are usually ER positive and associated with lobular carcinoma in situ (LCIS). HER2/neu overexpression is very rare. In contrast,poorly differentiated lobular carcinomas often lack hormone receptors, and may overexpress HER2/neu.12
More than 90% of Basal like breast cancers(BLBC) / Triple negative breast cancers (TNBC) exhibit an invasive ductal histology and high histological grade, present with high mitotic index and carry central necrotic zones and pushing borders as well as a conspicuous lymphocytic infiltrate. Additional characteristics of BLBC are frequent metaplastic elements and medullary /atypical medullary features.Recent reports confirm that very aggressive metaplastic tumours are BL by expression analysis.3
Although not synonymous with triple-negative breast cancer,the basal-like subtype commonly displays a triple negative phenotype often defined by a lack of estrogen receptor and progesterone receptor protein expression, with an absence of HER2/neu overexpression.13
6.3 Objectives of the study:
1) To study the histomorphological features of malignant epithelial
tumours of the breast.
2) To study ER,PR status and HER2/neu expression by IHC.
7. / MATERIALS AND METHODS:
7.1 Source of data:
Surgical biopsy and mastectomy specimens during the two years period from June 2011 to May 2013 diagnosed as carcinoma of the breast in the department of pathology JJM Medical College Davanagere will be included in the study.
7.2 Method of collection of data (including sampling procedure, if any):
The relevant clinical details will be collected from the patient records.Specimen will be fixed in 10% formalin and are subjected to thorough gross examination according to protocols.Representative bits will be taken from the tumour and accompanying lymphnodes and routinely processed to obtain paraffin sections of 5 micron thickness. Subsequently they will be stained by Hematoxylin and Eosin stain and special stains such as PAS, Mucicarmine , and Verhoeff`s stain will be employed when required .
One dedicated block from the tumour not fixed for more than 24 hrs in formalin will be used for IHC sections and stained for evaluating ER, PR receptors; and HER2/neu expression.
Statistical analysis:
Clinical features, gross and microscopic features; and IHC findings will be analysed. Chi-square test will be done.
Sample size : 50 cases
Inclusion criteria:
• Histologically proved carcinoma of breast.
Exclusion criteria:
• Benign lesions of the breast.
• Post chemotherapy biopsy specimens.
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly?
No.
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Yes
1. Maki DD, Grossman RI. Patterns of disease spread in metastatic breast carcinoma: influence of estrogen and progesterone receptors status. Am J Neuroradiol 2000;21:1064-66.
2. Helin HJ, Helle MJ, Kallioniemi O, Isola JJ. Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma correlation with histopathology and flow cytometry. Cancer 1989;63:1761-1767.
3. Gluz O, Liedtke C, Gottschalk N, Pusztai L, Nitz V, Harbeck N. Triple negative breast carcinoma-current status and future directions. Annals of Oncology 2009;20:1913-27.
4. Tumours of the breast. In: Tavassoli FA, Devilee P, Editors. World Health Organisation Classification of tumours. Pathology and genetics of tumours of the breast and female genital organs. IARC Press: Lyon 2003.P:11-111.
5. Nassar H, et al . Clinicopathologic analysis of invasive micropapillary differentiation in breast carcinoma. Modern Pathology 2001 ; 14 (9) : 836 -841.
6. Invasive duct carcinoma:assessment of prognosis, morphologic prognostic markers, and tumour growth rate. In: Rosen P.P . Rosen`s breast pathology. 3rd Edn, 2009: p358-404.
7. Cristofanilli .M, et al . Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. Journal Of Clinical Oncology 2005;23(1):41-48.
8. Tubular carcinoma . In: Rosen P.P . Rosen`s breast pathology. 3rd Edn, 2009:p 405-422.
9. Hammond M.E.H, et al. American society of clinical oncology/ College of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast carcinoma. Journal Of Clinical Oncology 2010;l28(16): 2784- 2795.
10. Donegan WL. Prognostic factors. Cancer supplement sept 1992;70(6): 1755-1761.
11. Lester SC. The breast. In: Kumar V, Abbas AK, Fausto N, Aster JC, Editors. Robbins and Cotran pathologic basis of disease. 8th Edn .Saunders:Philadelphia;2010.p. 1089-91.
12. Walker RA,Immunohistochemical markers as predictive tools for breast cancer. J Clin Pathol 2008;61:689-96.
13. Gruver AM, Portier BP, Tubbs RR. Molecular pathology of breast cancer.The journey from traditional practice toward embracing the complexity of a molecular classification. Arch Pathol Lab Med 2011 May;135:544-57.
9. / Signature of Candidate
10. / Remarks of Guide / .The presence of steroid hormone receptors in the tumour tissue has received considerable attention and respond favourably to hormone or endocrine therapy. Hence the study is undertaken.
11. / Name and Designation of
(In Block Letters)
11.1 Guide
11.2 Signature
11.3 Co-Guide (If any)
11.4 Signature
11.5 Head of Department
11.6 Signature / Dr.K.K.SURESH, M.D.
PROFESSOR,
DEPARTMENT OF PATHOLOGY,
J.J.M. MEDICAL COLLEGE,
DAVANGERE-577004.
Dr. S.S. HIREMATH, M.D.
PROFESSOR AND H.O.D,
DEPARTMENT OF PATHOLOGY
J.J.M. MEDICAL COLLEGE,
DAVANGERE-577004.
12. / 12.1 Remarks of the Chairman and Principal
12.2 Signature
[1]
[2]