I= ANALYSIS OF MORPHOLOGICAL IMMUNOHISTOCHEMICAL AND GENETIC PROGNOSTIC DETERMINANTS IN PREDICTING DISEASE FREE SURVIVAL OF BREAST CARCINOMA PATIENTS
Pakistan Research Repository Home
 

Title of Thesis
ANALYSIS OF MORPHOLOGICAL IMMUNOHISTOCHEMICAL AND GENETIC PROGNOSTIC DETERMINANTS IN PREDICTING DISEASE FREE SURVIVAL OF BREAST CARCINOMA PATIENTS

Author(s)
Syed Abdul Aziz
Institute/University/Department Details
University of Karachi, Pakistan./ Department of Genetic
Session
2001
Subject
Genetics
Number of Pages
361
Keywords (Extracted from title, table of contents and abstract of thesis)
morphological immunohistochemical, genetic prognostic determinants, breast carcinoma, breast cancer, tumor, epidermal growth factor receptor, cathepsin-d., proliferating cell nuclear antigen (pcna), inflammatory breast carcinoma (ibc), prefnancy/lactation associated breast carcinoma (pac)

Abstract
Breast cancer is an increasingly important cause of illness and death among women worldwide. In Pakistan also breast cancer is not only the commonest malignancy among women but it also occurs in a younger age compared to western population. This prospective study was conducted on 315 consecutive human breast biopsy and mastectomy specimens with lymph node sampling received from 1992 to 1997 with histological diagnosis of infiltrating ductal carcinoma breast. This study also included specimens from high-risk group i.e in-patient with informatory breast carcinoma and with pregnancy/lactation associated breast carcinoma. The major objective of the study was to assess the utility of novel prognostic markers in assessing the outcome of disease in Pakistani breast carcinoma patients. Novel prognostic markers studied included growth promoting genes products i.e C-crbB2 and EGFR. Tumour suppressor gene product i.e p53, proliferative market PCNA, along with a lysosomal protease i.e., Cathepsin-D. Established parameters and prognostic variables of breast cancer like age of the patient, menstrual status, tumour size histological grade, axillary lymph node status (distant metastases if any), Hormones Receptor (estrogen and progesterone) status were studied in parallel to these novel prognostic markers.

In this study p53, C-erbB2, EGFR and PCNA showed significant correlation with various established pathological variables as well as with disease free and overall survival. It was shown that p53, CerbB2, EGFR and PCNA were independent prognostic markers in both univariate and multivariate analysis. In our study cathepsin-D over-expression was not a good prognostic marker if only expression in tumour cells was taken into account.

In summary as breast cancer becomes a disease, which is now diagnosed and treated at an early stage in the west, these modern tools of investigation in parts of the world where this still presents in an advanced manner can serve as a useful method in understanding the biological behavior of breast cancer. This thesis is an attempt to identify predictive factors in breast cancer important for regional and distant spread as well as for disease free and overall survival in our clinical setting.

Download Full Thesis
3685.62 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
181.74 KB
2 1 General Introduction 27
1135.86 KB
  1.1 Introduction 27
  1.2 Ontogenetic (Cancer is Genetic Disease) 32
  1.3 Breast ( Normal ) 54
3 2 Materials and Methods
235.47 KB
  2.1 Materials and Methods 116
  2.2 Histological Grading of Tumour 116
  2.3 Antibodies and IHC procedure for ER/PR determination 117
  2.4 Methodology (for p53, C-erbB2, EFGR, CD and PCNA) 126
  2.5 Secondary Antibodies for Primary Monoclonal Antibodies 127
  2.6 Rabbit Anti Mouse lgG 127
  2.7 DNA Ploidy ands-phase fraction (SPF) 128
  2.8 Statistical Analysis 133
4 3 p53
238.83 KB
  3.1 Introduction 138
  3.2 Materials and Methods 148
  3.3 Results (1) 149
  3.4 Multivariate Analysis 153
  3.5 Discussion 158
5 4 C-erbB2 (HER-2/Neu-2).
330.8 KB
  4.1 Introduction 162
  4.2 Materials and Methods 167
  4.3 Results( 1) 172
  4.4 Results( II) 174
  4.5 Results( II) 175
  4.6 Discussion 179
6 5 Epidermal Growth Factor Receptor (EGFR).
202 KB
  5.1 Introduction 184
  5.2 Materials and Methods 189
  5.3 Results( 1) 192
  5.4 Results( II) 194
  5.5 Discussion 198
7 6 Cathepsin -D.
202.63 KB
  6.1 Introduction 201
  6.2 Materials and Methods 204
  6.3 Results( 1) 209
  6.4 Discussion 214
8 7 Proliferating Cell Nuclear Antigen (PCNA).
195.05 KB
  7.1 Introduction 218
  7.2 Materials and Methods 222
  7.3 Results( 1) 225
  7.4 Discussion 230
9 8 Inflammatory Breast Carcinoma (IBC).
360.33 KB
  8.1 Introduction 234
  8.2 Patients and Methods 239
  8.3 Results 244
  8.4 Multivariate Analysis 245
  8.5 Discussion 256
10 9 Prefnancy /Lactation Associated Breast Carcinoma (PAC)
271.84 KB
  9.1 Introduction 260
  9.2 Patients and Methods 265
  9.3 Results 269
  9.4 Discussion 278
11 10 General Discussion 283
78.35 KB
12 11 Recommendatio and Concerns 291
50.98 KB
  11.1 PUBLICATIONS FROM THIS THESIS 294
13 12 REFERENCES 295
56.9 KB
14 13 APPENDIX 354
563.92 KB