Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast.

BACKGROUND: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables. RESULTS: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively) without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively). The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021). CONCLUSIONS: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.

Relation of CD117 immunoreactivity and microvascular density in invasive breast carcinoma.

Background and Objective: In breast cancer, the expression of CD117 represents a highly controversial subject but the majority of studies have found decreased c-kit expression in malignant breast epithelium. A number of studies have reported that increased intratumoral microvessel density (MVD) is associated with poor prognosis in breast cancer. The aim of the study was to assess the relation of CD117 and MVD with other clinicopathological parameters in invasive breast carcinomas using the tissue microarray technique. Materials and Methods: A total of 126 cases of invasive breast carcinoma of different histological types and grades were collected from files of a pathology department during 2010. Clinicopathological and histological parameters were evaluated. Sections from formalin-fixed, paraffin-embedded tumor tissues microarray blocks were immunostained with CD117 and CD34. Statistical analysis of data was done using SPSS, version 16.0. Results: About 29% of invasive breast carcinomas were CD117 positive. There were significant differences between expression of CD117 in the tumor epithelial cells and age of the patient; tumor grade; tumor size, and LN metastasis. Also, there was significant relation between expression of CD117 in the tumor epithelial cells and MVD, expression of estrogen, and progesterone receptors. On multivariate analysis, the most important predictors of negativity of CD117 were tumor size and positive lymph node involvement. Conclusion: Lack of CD117 immunoreactivity in invasive breast carcinoma was associated with features of more aggressive tumor behavior as higher microvessel density, larger size, higher tumor grade, more lymph node metastasis, and negative estrogen and progesterone receptors.

Expression of survivin and p53 proteins and their correlation with hormone receptor status in Indian breast cancer patients.

Background : In invasive ductal carcinoma (IDC), many antiapoptotic and proapoptotic genes regulate disease outcome. Hormone receptor-mediated mechanisms have also been shown to prevent apoptosis. Therefore, relations between hormone receptor status and other molecular markers need further examination. Aims : In the present study, we analyzed the expression of apoptosis-regulating genes, viz., Survivin and mutant p53, in benign breast disease (fibroadenoma) and IDC patients. Results were then correlated with hormone receptor status of the patients. Material and Methods : Paraffin-embedded tissue samples from 63 untreated female patients with IDC and 32 female patients with fibroadenoma were used. Expression of Survivin and mutant p53 was evaluated using immunohistochemical staining method. Statistical Analysis : Fisher exact test and nonparametric correlation test (Spearman rank correlation test) were performed. Results : In fibroadenoma, 53% of patients expressed Survivin and 13% of patients expressed p53 protein. Statistically significant increase in Survivin and p53 protein expression was observed in carcinoma cases. Survivin expression correlated negatively with progesterone receptor (PR) status, but its expression was independent of estrogen receptor (ER) status. p53 expression showed negative correlation with both ER and PR status. Conclusions : Increased expression of Survivin and p53 in IDC patients and correlation with hormone receptors suggest that Survivin and p53 along with hormone receptors status are likely to contribute significantly to apoptosis resistance and may serve as therapeutic target that could increase the effectiveness of conventional breast cancer therapy.

Significance of HER-2/neu oncoprotein overexpression in invassive ductal breast cancer

To asses the frequency of HER-2/neu Oncoprotein over expression in invasive ductal breast cancer and correlate it with various prognostic parameters. Comparitive cross-sectional study was carriedout at department of pathology Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. Seventy two [72] formalin fixed paraffin embedded blocks of diagnosed invasive ductal carcinoma were retrieved and 5 m.m thick sections were cut and stained with H and E for the review of diagnosis and grading. The immunohistochemical staining was done on 4m.m thick sections by using Polyclonal rabbit anti HER-2 ZYMED USA, and ZYMED 2nd generation LAB-SA immunodetection system, to see the HER-/neu over expression. Section containing > 50% of tumor cells exhibiting intense circumferential cell membrane staining scored as positive. Thirty one [31%] positive over expression was observed. A statistically significant result [P<.05] was found between HER-2/neu over-expression and lymph node status and size of tumor. Oncoprotein HER-2/neu over expression is directly related to the lymph node status and size of the tumor. These patients may benefit from a more aggressive therapy like Herceptin and can also be used as a prognostic marker in the follow up of these patients

Molecular biology and gynecology: CD 36 and its interactions with tamoxifen

Tamoxifen (TAM) is an antiestrogenic drug widely used in breast cancer treatment. By using the Differential Display technique in normal and malignant breast tissues, before and during TAM therapy, we were able to demonstrate that expression of the CD36 gene is down-regulated by this drug. CD36 is a cell-surface glycoprotein that acts as a receptor for thrombospondin-1, oxidized-LDL and collagens type I and IV. Thrombospondin-1 is involved in invasion, metastasis and angiogenesis and therefore the down-regulation of CD36 induced by TAM, might correspond to an alternative mechanism of action of this drug. CD36 is also one of the receptors for the oxidized-LDL which in turn is involved in pathogenesis of arteriosclerosis; thus the down-regulation of CD36 during TAM might explain the at least in part the lower levels of myocardial infarction during its use.