Colorectal cancer is the fifth most common form of cancer in the United States and the third leading cause of cancer-related death in the Western world, in Iraq, the percentage of total cases of colorectal carcinoma was 4.45% of all body malignancies for both male and female and it is the seventh cause of death from cancer. HER\2neu oncogene which is a member of the tyrosine kinase family is found on normal cells, there is evidence that they are over expressed in many types of tumors. Clinically, HER2\neu amplification and/or over expression have been associated with poor prognosis in a number of tumors types such as breast and ovarian cancer in addition to other types of tumors, colorectal tumors are among others; also genetic instability has been proposed to be a driving force in colorectal carcinogenesis. Several studies in the past reported an increased risk of colorectal cancer in patients with BRCA1 germ-line mutations. Aim of the study was to assess the immunohistochemical expression of HER2\neu and BRCA1 in colorectal tumors (carcinoma and polyps) in correlation with some clinicopathological parameters (patient gender and age, tumors size and site, tumors types, grade, depth of invasion, tumor multiplicity and family history).
Materials and methods this retrospective study a total of (44) cases of colorectal tumors of which (22) cases CRC and (22) cases colorectal polyps were taken .Of these (44) cases, (30) cases were coloctomy and (14) cases were tissue biopsy. In addition to these cases there were (6) cases of non neoplastic colonic tissues. These non neoplastic colonic tissues included (4) cases of mild non specific colitis (endoscopic) and (2) post mortem cases were taken from the forensic medicine. All formalin fixed, paraffin-embedded tissues were retrieved from the archived files of the department" of pathology of Al-Kadhimiya teaching hospital and AL-Nasrya Teaching hospital / main laboratory and Gastrointestinal intestinal tract center for the period between Nov 2009- July 2010. The histopathological diagnosis had been revised and all cases were stained by immunohistochemical technique with HER2\neu and BRCA1 tumor markers. Rresults From the clinicopathological assessment, a total of (44) cases of colorectal tumors were included in this study, Histological examination of (H&E) sections revealed (22) cases colorectal carcinoma, and (22) cases colorectal polyps in addition to (6) non neoplastic colonic tissues. The male: female ratio was 1.4. The mean age of the patients was 44.42 ±2.53 years. The mean size of tumor was 2.59±0.54 cm (for patients with colorectal tumors). The colon was the most common site of colorectal tumors (benign and malignant) followed by the rectum. Most of the malignant cases were of non mucinous type (86%) and the most common grade was that of poorly differentiated adenocarcinoma. Considering the depth of invasion, T2 was the most frequent type (59% of the cases). HER2\neu immunostaining was clearly evident as brown membrane and cytoplasmic staining or brown cytoplasmic staining. HER2\neu over expressed in (36%) of colorectal tumors (benign and malignant), HER2\neu was expressed in (45%) of CRC, in (27%) of colorectal polyps and in (4) out of (6) non neoplastic colonic tissues. Pattern of staining was diffuse in (93%) of the cases and focal in (7%) of the cases of colorectal tumor. Positive staining was localized in the membrane and cytoplasm in most of the cases (93%) and cytoplasmic in (7%) of the cases of colorectal tumors.
HER2\neu was expressed more frequently in the colon in about (46%). HER2\neu was more frequently expressed in male (50%), in the age group of more than 40 years (43%) but the result was statistically not significant. HER2\neu was expressed more frequently in well differentiated adenocarcinoma (67%), in non mucinous adenocarcinoma (90%), in T2 (54%) and the mean size of tumors that expressed HER2\neu (Mean ± SEM) was 3.83 ± 1.29 although the results were statistically not significant. HER2\neu was expressed in (1) out of (2) cases with tubulovillous adenomatous polyps, in (3) out of (8) cases with tubular adenoma, in (1) out of (3) cases with villous adenoma, and in (1) out of (4) cases with inflammatory polyps.
BRCA1 immunostaining was found in (6%) of colorectal tumor and there were (14%) positive cases of colorectal polyps, the result was statically not significant. Pattern of staining was diffuse and localized in the cytoplasm in all the cases (100%). BRCA1 expressed more frequently in male (8%) and the mean age of the patients with BRCA1expression (Mean ± SEM) was 52 ±3.05 years the results were statistically not significant. The mean size of tumor that expressed BRCA1 (Mean ± SEM) was 1.36 ± 0.82 cm .The result was statistically not significant. BRCA1 was expressed more frequently in the colon (20%).BRCA1 was expressed in (1) out of (2) cases with tubulovillous adenomatous polyps, in (1) out of (3) cases with villous adenoma and in (1) out of (8) cases with tubular adenoma. Conclusions 1. Expression of HER2\neu in colorectal tumors (benign and malignant) is not infrequent phenomena (36% of colorectal tumors were showed HER2\neu expression). 2. Low expression of BRCA1 in colorectal tumors (6% of colorectal tumors were showed BRCA1 expression) and there was no significant correlation of BRCA1 expression with clinicopathological parameters (age, gender, tumors types, site and size).