Nasir Aejaz, Kaiser Hans E, Boulware David, Hakam Ardeshir, Zhao Helena, Yeatman Timothy, Barthel James, Coppola Domenico
H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, USA.
Clin Colorectal Cancer. 2004 Feb;3(4):243-7. doi: 10.3816/CCC.2004.n.005.
Cyclooxygenase-2 (COX-2) has been identified as a potential target for prevention and therapy of human colorectal cancers (CRC) and other cancers. Because right-sided colon cancers (RSCCs) exhibit clinicopathologic and genetic differences from left-sided colorectal cancers (LSCRCs), determination of COX-2 status in these subsets of CRCs may be clinically relevant in designing COX-2 inhibitor trials for CRC and in subsequent assessment of objective therapeutic response to such therapy. Thirty-six primary CRC resection specimens (18 left, 18 right) from 36 patients were evaluated. Representative tumor sections were subjected to immunohistochemical analysis of COX-2. A semiquantitative system was used to score cytoplasmic COX-2 immunostaining. The tumors were considered COX-2 positive if more than 10% tumor cells showed COX-2 staining. Clinicopathologic and COX-2 data were compared for LSCRCs versus RSCCs. All 18 LSCRCs and 13 of 18 (72%) RSCCs were well to moderately differentiated. Overall rates of COX-2 positivity for the LSCRCs versus RSCCs were 67% (12 of 18) and 33% (6 of 18), respectively (P = 0.04). Furthermore, 11 of 12 (92%) COX-2 positive LSCRCs and 3 of 6 (50%) COX-2 positive RSCCs were stage II-IV at resection. All 12 COX-2 positive LSCRCs were associated with advanced primary tumor and 4 of 12 (33%) LCRCs had distant metastases. These associations could not be evaluated for the RSCCs because of the limited number of COX-2 positive cases. The more frequent expression of COX-2 in LSCRCs as compared with RSCCs supports the hypothesis that COX-2 expression may be related to genetic alterations specific to right- or left-sided CRCs. Further studies are needed to elucidate such relationships. Our data also suggest that stratification of patients with CRC into right- and left-sided subsets may be important in optimal patient selection for COX-2 inhibitor therapy and for subsequent assessment of objective therapeutic response.
环氧化酶-2（COX-2）已被确定为预防和治疗人类结直肠癌（CRC）及其他癌症的潜在靶点。由于右侧结肠癌（RSCC）在临床病理和基因方面与左侧结直肠癌（LSCRC）存在差异，因此在这些CRC亚组中确定COX-2状态对于设计CRC的COX-2抑制剂试验以及随后评估对此类治疗的客观治疗反应可能具有临床意义。对36例患者的36个原发性CRC切除标本（18个左侧，18个右侧）进行了评估。对代表性肿瘤切片进行COX-2免疫组化分析。采用半定量系统对细胞质COX-2免疫染色进行评分。如果超过10%的肿瘤细胞显示COX-2染色，则肿瘤被视为COX-2阳性。比较了LSCRC与RSCC的临床病理和COX-2数据。所有18例LSCRC和18例RSCC中的13例（72%）为高分化至中分化。LSCRC与RSCC的COX-2阳性总体率分别为67%（18例中的12例）和33%（18例中的6例）（P = 0.04）。此外，12例COX-2阳性LSCRC中的11例（92%）和6例COX-2阳性RSCC中的3例（50%）在切除时为II-IV期。所有12例COX-2阳性LSCRC均与原发性肿瘤进展相关，12例LCRC中有4例（33%）有远处转移。由于COX-2阳性病例数量有限，无法对RSCC进行这些相关性评估。与RSCC相比，COX-2在LSCRC中更频繁的表达支持了COX-2表达可能与右侧或左侧CRC特有的基因改变有关的假设。需要进一步研究来阐明这种关系。我们的数据还表明，将CRC患者分为右侧和左侧亚组对于COX-2抑制剂治疗的最佳患者选择以及随后对客观治疗反应的评估可能很重要。
