RESUMO
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.
RESUMO
Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.
