Frequency of Her2/neu expression in colorectal adenocarcinoma: A study from developing South Asian country

Abstract

Background: Human Epidermal Growth Factor (Her-2/neu) has strong therapeutic implications in certain cancers like breast and gastric cancer. Literature on its frequency in colorectal cancer is scarce. In this study, we have investigated the frequency of Her-2/neu expression in colorectal adenocarcinomas and its association with various clinicopathological variables. Methods: A total of 95 patients who underwent colonoscopic biopsy or colectomy were studied after Institutional Ethical Approval. Hematoxylin & eosin (H&E) staining was performed on all the tissue sections. Expression of Her-2/ neu was investigated by immunohistochemistry using α-Her-2 antibody. In order to quantify Her-2/neu expression, three criterias were applied that includes the pattern of staining, intensity of staining and percentage of tumor cells stained. Furthermore, its association was seen with various clinicopathological variables including age, gender, histopathological type, grade and stage of the tumor. Data was entered and analyzed using SPSS version 21. A pvalue of < 0.05 was considered as significant. Results: From the total of 95 cases, 75 (78.9 %) cases showed Her-2/neu expression. Pattern of Her-2/neu staining was significantly associated with the grade of colorectal cancer depicting cytoplasmic Her-2/neu expression higher in low grade (50 %) while membranous Her-2/neu expression more in high grade colorectal cancer (45 %) (P-value = 0.030). Pattern of Her-2/neu staining was also significantly associated with the type of colorectal cancer representing membranous Her-2/neu expression to be more common in mucinous type (38.5 %) while cytoplasmic Her-2/neu expression to be more frequent in non mucinous type (42.7 %) of colorectal cancer (p-value = 0.024). We observed a significant association between percentage of cells stained & tumor type, with score 3+ maximum in non mucinous type of colorectal cancer (p-value = 0.006). Conclusion: Her2/neu is considerably expressed in colorectal adenocarcinoma in Pakistani population. Our findings indicate a significant strong association of cytoplasmic Her-2/neu expression with low grades and membranous Her-2/ neu expression with high grades of colorectal cancer. These findings add to the body of information & may help in conducting clinical trials in future to explore its therapeutic significance as well.

Differential Expression of HER2 and SKP2 in Benign and Malignant Colorectal Lesions

“…In agreement with Song et al, (2014), Shabbir et al, (2016) and Sayadnejad et al, (2017) we did not find a significant link between HER2 expression and tumor stage or lymph node metastasis (TN stage). On the contrary, Elwy et al, (2012) and Heppner et al, (2014) reported a significant association with higher stages and positive nodal status.…”

“…Half and his colleagues, 2004 found a significant relation between the cytoplasmic HER2 staining and tumor differentiation. Also, Shabbir et al, (2016) concluded a significant strong association between cytoplasmic HER2 expression and low grades of CRC, as well as between membranous HER2 expression and high grade CRC.…”

“…Percentage of stained cells: ≤10% stained cells= score 0, 10-40 % stained cells = score 1+. Both 0 and 1+ scores were considered negative, 40-70% stained cells = score 2+, which was considered equivocal, and >70% stained cells = score 3+, which was considered positive (Shabbir et al, 2016).…”

HER2 overexpression/amplification status in colorectal cancer: a comparison between immunohistochemistry and fluorescence in situ hybridization using five different immunohistochemical scoring criteria

“…Therefore, the IRS-p ranges from 0 to 9, while the IRS-m ranges from 0 to 24. Then, both IRS-p and IRS-m were classi ed into IHC 1+ (IRS-p score 1-2, IRS-m score 1-3), IHC 2+ (IRSp score 3-7, IRS-m score 4-8), and IHC 3+ (IRS-p score 8-9, IRS-m score [12][13][14][15][16][17][18][19][20][21][22][23][24]. IHC scores of 0 and 1+ were considered as being "HER2 negative", IHC score of 2+ was considered as being "HER2 equivocal", and IHC score of 3+ was considered as being "HER2-positive".…”

“…They de ned three conditions of HER2 positivity as follows (HERACLES criteria): (1) a HER2 immunohistochemical (IHC) 3 + score in ≥ 50% of CRC cells; (2) a HER2 IHC 3 + score in 10%-50% of the CRC cells, and a uorescence in situ hybridization (FISH) HER2/CEP17 ≥ 2.0 in ≥ 50% of CRC cells; (3) more than 50% of CRC cells with a HER2 IHC 2 + score and a FISH HER2/CEP17 ≥ 2.0. However, to date, HER2 diagnostic criteria for gastroesophageal adenocarcinoma (GEA criteria) 16 or other independent HER2 IHC scoring systems 21,22 have also been used in CRC HER2 studies. Moreover, the prognostic role of HER2 in CRC remains controversial.…”