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

## TL;DR

This study compares colorectal cancer in rectosigmoid and other colonic locations, finding differences in age, survival, and protein expression that may affect prognosis and treatment.

## Contribution

This is the first study to compare P16Ink4a and P57KIP2 immunohistochemical expression in rectosigmoid CRC versus other colonic CRC and their relationship to clinical outcomes.

## Key findings

- Rectosigmoid CRC cases had lower age <40 years, higher MMR proficiency, and worse survival compared to other colonic CRC.
- P16Ink4a and P57KIP2 expressions were higher in rectosigmoid CRC, but these markers were more predictive of outcomes in other colonic CRC.
- P16Ink4a positivity in other colonic CRC was linked to higher recurrence and mortality hazards, while P57KIP2 positivity was linked to lower mortality hazard.

## 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.