Proliferative Activity in Primary Breast Carcinomas is a Salient Prognostic Factor

AimBreast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.MethodsExpression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.ResultsExpression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).ConclusionsThis study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.

Download Full-text

Cell Kinetics and Tumor-Associated Antigen Expression in Human Mammary Carcinomas

The International Journal of Biological Markers ◽

10.1177/172460089100600304 ◽

1991 ◽

Vol 6 (3) ◽

pp. 159-166 ◽

Cited By ~ 1

Author(s):

A. Contegiacomo ◽

R. Mariani Costantini ◽

R. Muraro ◽

P. Battista ◽

C. Valli ◽

...

Keyword(s):

Cell Proliferation ◽

Proliferative Activity ◽

Antigen Expression ◽

Breast Carcinomas ◽

Cellular Kinetics ◽

Tumor Associated Antigen ◽

Antigenic Expression ◽

High Proliferative Activity ◽

Antigenic Phenotype ◽

Intense Immunoreactivity

Twenty-six primary breast carcinomas were studied to evaluate cell proliferation as assessed by thymidine labeling index (TLI), and antigenic phenotype, as defined by immunohistochemistry using eight monoclonal antibodies (MAbs) to tumor-associated antigens (TAAs). The majority of tumors had low TLI values. Reactivity to MAbs B72.3, CC49, CC83 (anti TAG 72), COL-12 (anti CEA) and MOv2 (against a tumor-associated mucoprotein) was restricted to < 50% of the tumors studied, while MAbs B1.1 (anti CEA), MBrl and MBr8 (to tumor-associated carbohydrates) reacted with > 50% of the cases. Correlations between expression of TAAs and proliferative activity showed that the tumors could be divided into three groups, two characterized by either high proliferative activity and absence of antigenic expression or low proliferative activity and strong antigenic expression, and the third showing no relation between these two biological features. We defined two antigenic phenotypes associated with specific cellular kinetics: one characterized by negative immunoreaction with MAbs, CC49, CC83 and COL-12 and high proliferative activity; the other characterized by intense immunoreactivity with these antibodies and low proliferative activity. The data suggest that cell proliferation and antigenic phenotype may define biologic subsets of breast carcinomas

Download Full-text

Immunohistochemical Distribution of Mucinous-like Carcinoma Associated Antigen (MCA) in Breast and Non-breast Cancer: Comparison with other Biological Parameters

The International Journal of Biological Markers ◽

10.1177/172460089000500307 ◽

1990 ◽

Vol 5 (3) ◽

pp. 138-144 ◽

Cited By ~ 7

Author(s):

M. Martinazzi ◽

F. Crivelli ◽

C. Grassi ◽

C. Zampatti

Keyword(s):

Proliferative Activity ◽

Progesterone Receptors ◽

Growth Fraction ◽

Human Tissues ◽

Biological Parameters ◽

Breast Carcinomas ◽

Epithelial Growth Factor ◽

Cancer Tissues ◽

P 53 ◽

Epithelial Growth

The present study reports the immunohistochemical reactivity of the monoclonal antibody b-12 (MAb b-12) with malignant human tissues. 173 neoplastic tissues were tested: MAb b-12 stained all breast carcinomas independently of their histology, with different patterns within the various type of cancer. Some other carcinomas (stomach, bowel, ovary, lung, endometrium), were also reactive even if the fraction of positive cells was lower. A comparison between the histological localization of MCA and that of CEA was performed; anti-CEA antibodies stained the cancer tissues with different reactivity and showed different percentages of positivity. MCA expression was also compared with other biological parameters such as the presence of estrogen receptors (ER), progesterone receptors (PgR), epithelial growth factor receptors (EGF-R), and oncoprotein p-53 which is encoded by the oncogene N-myc. The proliferative activity was also evaluated by measuring the growth fraction (GF) using the antibody Ki67. Any correlation was demonstrated between MCA and these parameters except for growth fraction as revealed by Ki67 antibody.

Download Full-text

MIB-1 Proliferative Activity Is a Significant Prognostic Factor in Primary Thick Cutaneous Melanomas

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12312431 ◽

1995 ◽

Vol 105 (1) ◽

pp. 22-26 ◽

Cited By ~ 69

Author(s):

Jennifer A. Ramsay ◽

Lynn From ◽

Neill A. Iscoe ◽

Harriette J. Kahn

Keyword(s):

Prognostic Factor ◽

Proliferative Activity ◽

Significant Prognostic Factor ◽

Mib 1

Download Full-text

Flow cytometry in primary breast carcinomas. Prognostic impact of proliferative activity

Breast Cancer Research and Treatment ◽

10.1023/a:1006451908322 ◽

2000 ◽

Vol 62 (2) ◽

pp. 117-126 ◽

Cited By ~ 21

Author(s):

Jean-Jacques Michels ◽

Françoise Duigou ◽

Jacques Marnay

Keyword(s):

Flow Cytometry ◽

Proliferative Activity ◽

Prognostic Impact ◽

Breast Carcinomas

Download Full-text

Low proliferative level is a poor prognostic factor for colon adenocarcinoma

Kazan medical journal ◽

10.17816/kmj1518 ◽

2014 ◽

Vol 95 (3) ◽

pp. 378-382

Author(s):

G A Raskin ◽

S V Petrov

Keyword(s):

Prognostic Factor ◽

Proliferative Activity ◽

Single Case ◽

Cancer Recurrence ◽

Colon Adenocarcinoma ◽

Tumor Stage ◽

Ki 67 ◽

Poor Prognostic Factor ◽

Significant Difference ◽

Primary Colon

Aim. To match up the proliferative activity of colon adenocarcinoma cells with tumor stage and survival rate. Methods. Ki-67 protein expression was evaluated by immunohistochemical methods in 217 patients with primary colon adenocarcinoma. After epitope retrieval and endogenous peroxidase inhibiting by 3% solution of hydrogen peroxide, histologic samples were stained by antibodies to Ki-67 protein (clone SP6, dilution 1:300) and polymer systemic detection with diaminobenzidine as a chromogenic substrate. Nuclear counterstain was performed using Mayer’s hematoxylin solution. Results. Assessment of colon adenocarcinoma proliferative activity showed a significant difference between the number of cases with high (70%) and relatively low (≤30%) proliferative levels in groups with metastatic cancers and non-metastatic tumors. In patients with no relapses, colon adenocarcinoma proliferative activity assessment showed proliferation level exceeding 70% in 21 (95%) out of 22 cases, in a single case proliferation level of 60% was found according to Ki-67, no cases of proliferation level lower than 50% was found. Statistical analysis showed that proliferative activity was significantly lower in patients with metastatic colon adenocarcinoma compared to cases of adenocarcinoma without metastases (p= 0.0019). We observe one clinical case of aggressive colon adenocarcinoma with omental, peritoneal, paraumbilical metastases in 28-year old patient, in whom proliferative activity by Ki-67 was measured as 20%. Conclusion. Low proliferative level in colon adenocarcinoma is a poor prognostic factor for possible metastasing and cancer recurrence.

Download Full-text

Evaluation of Smad2/3 and Smad4 as inhibitors of estrogens and Ski protein as a predictive factor in T1, T2 N0 breast carcinomas

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1543 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1543-1543

Author(s):

D. S. Koumoundourou ◽

T. I. Kassimatis ◽

E. Tzorakoleftherakis

Keyword(s):

Prognostic Factor ◽

Prognostic Value ◽

Independent Prognostic Factor ◽

Negative Regulator ◽

Clinicopathological Parameters ◽

Breast Carcinomas ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Smad Proteins ◽

Ski Protein

1543 Background: Smad proteins are TGF-β intracellular substrates, and Ski protein is a negative regulator of TGF-pathway. Tamoxifen's inhibition in breast cancer cells is mediated through TGF-β and Smad proteins. The purpose of our study was to investigate the activation of Smad2/3, Smad4, and Ski proteins in breast carcinomas and correlate their expression with each other and with hormonal receptors, as well as with other clinicopathological parameters such as the tumor size and grade, and the Distant Disease Free and the Overall Survival. Methods: One hundred forty-seven paraffin-embedded specimens from 22 in situ and 125 invasive ductal node-negative carcinomas were used, for which we had a mean follow-up time of 96 months. ER and PR status, as well as the expression of Smad2/3, Smad4, and Ski proteins were evaluated using immunohistochemistry. Staining of 5% of the tumor cells was adopted as a threshold. SPSS13 for windows was used for the statistical analysis of the results. Results: Smad2/3 and Smad4 were strongly correlated with each other (p < 0,001) and inversely correlated with patients’ DDFS (Kaplan-Meier plots, p = 0,004 for Smad2/3 and p = 0,026 for Smad4) and OS (Kaplan-Meier plots, p = 0,034 for Smad2/3 and p = 0,017 for Smad4). Smad2/3 was proved to be an independent prognostic factor in grade 1 tumors, while Smad4 was inversely correlated with PR expression (p = 0,028) and had a strong prognostic value in ER+ tumors (p = 0,02). Ski protein had a strong association with tumor grade (p < 0.001) and was found to be an independent prognostic factor in Cox regression analysis (p = 0,006, exp(B) = 4,98). Conclusions: Smad 2/3 and Smad 4 not only are tumor suppressor molecules, but also inhibit ER dependent gene expression. This inhibition is lost when Smad's expression is reduced, and that is a potent explanation for Smad 4 prognostic value in ER positive tumors. Moreover the correlation with PR expression, may be due to the fact that PR is an indicator of ER pathway's integrity and also to PR's enallaktiki activation by ER-β. From the other hand, Ski protein acts as an oncogene in breast carcinogenesis and contributes to the development of a more aggressive tumor phenotype. No significant financial relationships to disclose.

Download Full-text