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Abstract：
Background One unique criterion of colorectal carcinoma (CRC) is the different locations within the colorectum. Different CRC sidedness/locations could have distinct criteria, including risk factors, morphological features, genetic alterations, prognostic factors, and clinical outcomes. Nearly half of the CRC cases occur in the rectal-sigmoid locations, while other colonic locations constitute the other half. Investigating specific protein expression patterns in the rectosigmoid CRC (rsCRC) compared to other colonic (ocCRC) locations helps understand the disease pathogenesis, predict prognosis, and design personalized treatments. This study is the first to compare P16Ink4a and P57KIP2 immunohistochemical (IHC) expression in rsCRC to ocCRC and examine their relationship to disease outcomes in both locations. Materials and methods A comparative cross-sectional study used tissue microarray slides from rsCRC and ocCRC that were immunohistochemically stained by anti-P16Ink4a and P57KIP2 antibodies. A semi-quantitative scoring system classified each marker\'s expression as positive or negative. The statistical analysis compared clinicopathological features, P16Ink4a and P57KIP2 expressions, and their relationship to clinical outcomes in rsCRC and ocCRC cases. Results One hundred fifty CRCs were distributed into the rsCRC cases (n=86, 57.3%) and the ocCRC cases (n=64, 42.7%). The rsCRC cases had a significantly lower age <40 years (P=0.002), higher frequency of mismatch repair (MMR) proficient status (P=0.003), and perineural invasion (P=0.008), with lower disease-free (DFS) and overall survival (OS) (P=0.03, and P=0.015, respectively). Significantly higher positive P16Ink4a and P57KIP2 IHC expressions were found in the rsCRCs compared to the ocCRCs (P=0.02, and P=0.03, respectively); however, their relationship to the hazards (HR) of recurrence (HR=4.02, P=0.058, and HR=0.36, P=0.14, respectively) and mortality (HR=2.56, P=0.21, and HR=0.23, P=0.58, respectively) in the rsCRC group was statistically nonsignificant. In the ocCRC group, P16Ink4a positivity was significantly associated with a higher disease recurrence and mortality hazard (HR=8.19, P=0.007, and HR=5.57, P=0.037, respectively), while P57KIP2 positivity was significantly associated with a lower mortality hazard (HR=0.12, P=0.027). Conclusion The rsCRCs differ from ocCRCs in clinicopathological criteria and protein expression patterns. Though P16Ink4a and P57KIP2 IHC expressions are higher in the rsCRC than in the ocCRC, their value as outcome predictors is higher in the ocCRCs rather than the rsCRCs. P16Ink4a and P57KIP2 can act as prognostic markers and be suitable targets for therapy modulation in the ocCRC group.
摘要：
背景技术结肠直肠癌(CRC)的一个独特标准是结肠直肠内的不同位置。不同的CRC侧面/位置可能有不同的标准，包括风险因素，形态特征,遗传改变,预后因素，和临床结果。几乎一半的CRC病例发生在直肠乙状结肠位置，而其他结肠位置构成另一半。与其他结肠（ocCRC）位置相比，研究直肠乙状结肠CRC（rsCRC）中特定的蛋白质表达模式有助于了解疾病的发病机理。预测预后，并设计个性化的治疗方法。这项研究是第一个比较rsCRC和ocCRC中P16Ink4a和P57KIP2免疫组织化学（IHC）表达，并检查它们与两个位置的疾病结局的关系。材料和方法比较性横截面研究使用来自rsCRC和ocCRC的组织微阵列载玻片,其通过抗P16Ink4a和P57KIP2抗体进行免疫组织化学染色。半定量评分系统将每个标记的表达分类为阳性或阴性。统计分析比较临床病理特征，P16Ink4a和P57KIP2表达式，以及它们与rsCRC和ocCRC病例临床结局的关系。结果150例CRC分布在rsCRC病例（n=86，57.3%）和ocCRC病例（n=64，42.7%）中。rsCRC病例年龄<40岁(P=0.002),较高的错配修复频率（MMR）熟练状态（P=0.003），和神经周浸润（P=0.008），无病生存率（DFS）和总生存率（OS）较低（分别为P=0.03和P=0.015）。与ocCRC相比，rsCRC中的P16Ink4a和P57KIP2IHC阳性表达明显更高（分别为P=0.02和P=0.03）；然而，rsCRC组患者的复发风险(HR=4.02,P=0.058,HR=0.36,P=0.14)和死亡率(HR=2.56,P=0.21,HR=0.23,P=0.58)之间的关系无统计学意义.在ocCRC组中，P16Ink4a阳性与较高的疾病复发和死亡风险显著相关(分别为HR=8.19,P=0.007,HR=5.57,P=0.037),而P57KIP2阳性与较低的死亡风险显著相关(HR=0.12,P=0.027).结论rsCRCs在临床病理标准和蛋白表达模式上与ocCRCs不同。尽管rsCRC中的P16Ink4a和P57KIP2IHC表达式高于ocCRC，它们作为结果预测因子的价值在ocCRC中高于rsCRC.P16Ink4a和P57KIP2可以作为预后标志物，并且是ocCRC组中治疗调节的合适靶标。
