Histopathological characteristics of breast cancer and evaluation of ER alpha and Her-2neu using immunohistochemical and RT-PCR techniques

Oestrogen receptor [ER] and HER [human epidermal growth factor receptor] family signaling pathways are fundamental to guide treatment and determine prognosis. Categorizing breast cancer tumors as ER and Her-2 positive or negative is usually performed by immunohistochemistry [IHC], however the technique lacks standardization in handling tissues, staining techniques, and scoring systems. The current study aimed to compare the conventional IHC and the RT-PCR techniques in assessing the ER-alpha status in breast cancer. It also validates the application of RT-PCR technique in detecting the Her-2/neu status. The study included 40 patients with IDC [NOS] [invasive ductal carcinoma; not otherwise specified]. Breast tissue specimens were collected at the time of the elective surgery. Specimens were subjected to routine pathological examinations. ER alpha and PR receptor status; assessed by immunohistochemical staining. RNA was extracted, reverse transcribed, and amplified by PCR using ER alpha and HER-2 specific primers. Relative expression was detected

Elevated serum and tissue VEGF associated with poor outcome in breast cancer patients

Vascular endothelial growth factor [VEGF] has a potent angiogenesis functions in experimental models, although their role in the progression of human breast cancer is unclear. The aim of the current study was to examine the expression pattern of VEGF in serum and tissues of breast cancer patients, examine the tumor vascular characteristic by counting the blood vessels to assess microvessles density [MVD] and conduct correlations between the expressions of growth factor in relation to patient's clinicopathological data and survival. One hundred and twenty untreated patients with breast cancer were included in the study and followed for 4 years and 30 females with benign breast lesions matched with age and menstrual state as [control group]. In this work we examine serum and tissue expression of VEGF by enzyme linked immune absorbent assay [ELISA] and immunoperoxidase technique respectively. Microvessels density were assessed and correlated with expression of growth factors. The mean serum level of VEGF elevated in breast cancer patients before surgery was significantly higher when compared to that in patients with benign breast lesions or in the same patient after surgery. There was positive correlation between serum and tissue VEGF. Serum and tissue vascular endothelial growth factor was strongly associated with grade III tumor, large tumor size, positive lymph node, negative hormone receptor status, +ve HER[2] neu and poor survival, the data of the present study showed significant increase in mean serum level of VEGF in patients with positive vascular invasion P: 0.013. VEGF appear to play an important role in progression of breast carcinoma and to have significant impact on patient prognosis and can be used to identify a subset of breast cancer at higher risk for development of recurrence and distant metastasis

Hormone receptors and her-2 expression in early breast ductal carcinoma; frequency, and impact on outcome of tamoxifen therapy

Recent clinical data have suggested that efficacy of tamoxifen in reducing the risk of local recurrence in breastductal carcinoma [DC] is limited to estrogen receptor [ER] positive lesions, however, a group of these patientshave conflicting results. The purpose of this study was to assess the frequency of Progesterone receptor [PR] and HER-2overexpression in [ER] positive breast ductal carcinoma, in relation to each other, to important prognostic factors,and to correlate the results to patients' response to tamoxifen.Methods: We have analyzed the clinical outcome of selected 100 cases of ER +ve breast ductal carcinoma atclinical stage O-II, represented to pathology and oncology departments, Medical Research Institute in the period January-March 2002, with a follow up period of four years [median 34.5 months]. The patients were treated with standard adjuvant therapy of Tamoxifen [alone or after chemotherapy]. For each case ER, PR and HER-2 wereimmunohistochemically determined. In 100 cases ofER+ breast duct carcinoma, 89% were PR+, and 22% were HER-2+ve. There was a strongpositive correlation between ER and PR [p<0.001], and strong negative correlation between both hormones andHER-2 [p<0.001]. It was found that ER+/PR - tumors were more frequent in older patients [P=<0.001] and withhigher tumor grade [P=0.018], while ER+/HER-2 +ve tumors were significantly associated with patient's age [P=0.005], tumor size [P<0.003] and tumor grade [P< 0.001].On median follow up period of 34.5 months; the overall recurrence rate was 6%, and was restricted toHER-2[3+] +cases. ER+/PR tumors express higher levels of HER-2 and display more aggressive features thanER+/PR+ tumors. Overexpression of HER-2 might limit or negate the beneficial effects of tamoxifen in ER+vebreast DC

Apoptosis, proliferation, and FAS/FASL expression in pancreatic adenocarcinoma

Deregulation of normal cell cycle machinery is integral to neoplastic growth. There is now compelling evidence implicating the loss of cell kinetic balance in the development and progression of most human cancers, including pancreatic carcinoma which caries extremely poor prognosis. Understanding the pathogenesis of pancreatic cancer seems to be of great value in order to determine the mechanisms of the aggressive growth and metastasis. As the tumor growth depends upon the balance between apoptosis and proliferation, herein, we analyzed by immunohistochemistry the expression of Fas and FasL in 20 operative specimens of pancreatic ductal adenocarcinoma. The apoptotic index [AI] was evaluated by TUNEL in relation to the proliferation index [PI] as estimated by Ki67 aiming to correlate [AI and PI] with clinicopathologic variables and apoptosis-regulating proteins Fas and Fas-L. Fas and FasL were inversely correlated and were detected in 40% and 65% of cases respectively. The mean apoptotic index [AI] was 1.40 +/- 0.74%, and the mean proliferation index [PI] was 42.7 +/- 14%. Fas and AI were closely associated and decreased significantly in higher tumor grade and stage; whereas, FasL and PI increased significantly in higher grade and stage. Tumor infiltrating lymphocytes [TIL] showed higher mean apoptotic index in FasL positive than FasL negative tumor tissues. Therefore, it could be suggested that the apoptotic and proliferation indices could be useful prognostic markers in pancreatic ductal adenocarcinoma. Fas expression plays a key role in apoptosis in pancreatic cancer and FasL expressing carcinomas induce marked apoptosis in TIL allowing them to evade immune surveillance. Therefore, we recommend designing new therapeutic approaches for pancreatic adenocarcinoma based on reinforcement of Fas/FasL-induced tumor apoptosis