HER2-neu Expression and Survival in Colorectal Cancer in the South of Egypt; Immunohistochemistry and Genetic Study.

BACKGROUND: Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in different types of cancer is HER2. However, the role of HER2 in CRC and its relation with clinicopathological features and survival is conflicting. We hypothesize that HER2 has different patterns of expression in CRC which may affect the prognosis of patients. MATERIAL & METHODS: We studied sixty specimens of colorectal carcinoma for HER2 immunohistochemistry and gene amplification and correlate it with clinicopathological features and patients` survival. RESULTS: Our data showed that negative HER2 expression was statistically associated with female gender (P = 0.010) and low & intermediate tumor budding (P = 0.030). There was a statistically significant relation between HER2 IHC and HER2 FISH amplification (P=0.000). Although neither HER2 immunoexpression and FISH amplification showed significant relation with overall survival nor disease free survival, HER2 amplified CRCs tended to have a worse survival compared with negative CRCs (40 months versus 50 months). The presence of male gender, lymphovascular invasion, nodal metastasis and distant metastasis (P = 0.013, 0.006, 0.006 and 0.000 respectively) were significantly statistically associated with poor overall survival. The presence of tumor grade III and high tumor budding (P = 0.035 and 0.007 respectively) were significantly statistically associated with shorter disease free survival. CONCLUSIONS: Our results showed that HER2 IHC 3+ staining is highly predictive of HER2 gene amplification in colorectal carcinomas. There is a tendency towards poorer prognosis in amplified HER2 CRC cases.

Increased glomerular Bax/Bcl2 ratio is positively correlated with glomerular sclerosis in lupus nephritis.

INTRODUCTION: The role of intrinsic pathway of apoptosis in pathogenesis of lupus nephritis (LN) is still not clear. We investigated the relation between the expression of two major proteins of the intrinsic pathway of apoptosis; bcl2 as an antiapoptotic protein and bax as a proapoptotic one; in renal tissue of LN. METHODS: The study included fifty paraffin embedded renal tissue obtained from renal biopsy specimens of LN patients (8 cases class II, 10 cases class III, 21 cases class IV and 11 cases class V) and five paraffin embedded apparently normal renal tissue obtained from nephrectomy specimens due to renal neoplasms as a control group. Immunohistochemical staining for bcl2 and bax antibodies was done. Ki67 immunohistochemical staining was done for class III and IV to assess the degree of proliferation. The number of intraglomerular bcl2, bax and ki67 positive cells per glomerular cross section was evaluated for each case. The results were analysed in different LN classes and correlated to different glomerular lesions. RESULTS: The expression of bax and bcl2 proteins was higher in LN glomeruli compared to normal. The expression of bcl2 was significantly higher in class IV and was correlated to the degree of endocapillary hypercellularity. The bax to bcl2 ratio was significantly correlated to the percentage and degree of glomerular sclerosis. CONCLUSION: The intrinsic pathway of apoptosis interfere in the pathogenesis of lupus glomerulonephritis. The balance between bax and bcl2 proteins might have a role in regulating the progression of glomeruli from proliferative to sclerotic state.