Differences in Clinicopathological Features, P16Ink4a and P57KIP2 Immunohistochemical Expressions, and Survival Between Colorectal Carcinoma in Rectosigmoid and Other Colonic Locations.

Abstract

Background One unique criterion of colorectal carcinoma (CRC) is the different locations within the colorectum. Different CRC sidedness/locationscould 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) proficientstatus (P=0.003), andperineural 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.