Prognostic Value of LC3B and p62 Expression in Small Intestinal Adenocarcinoma

Autophagy, a mechanism that maintains cellular homeostasis, is involved in tumor cell growth and survival in cancer, and autophagy inhibitors have been tested clinical trials for anticancer therapy. To elucidate the clinical and prognostic implications of autophagy in small intestinal adenocarcinoma (SIAC), we assessed the expression of autophagy markers, LC3B and p62, in 171 surgically resected primary SIACs using automated quantitative analysis. Positive LC3B, p62 nuclear (p62Nu), and p62 cytoplasmic (p62Cy) expression was observed in 23 (13.5%), 52 (30.4%), and 43 (25.1%) carcinomas, respectively. LC3B+ expression was correlated with undifferentiated carcinoma (p < 0.001) and high histologic grade (p = 0.029). The combined expression of LC3B and p62Nu (LC3+/p62Nu+) was related to the older age of patients (p = 0.017), undifferentiated carcinoma (p < 0.001), and high grade (p = 0.031). LC3B+ (p = 0.006), p62Cy+ (p = 0.041), or p62Nu+ (p = 0.006) expression were associated with worse survival. In addition, SIAC patients with either LC3B+/p62Nu+ (p = 0.001) or LC3B+/p62Cy+ (p = 0.002) expression had shorter survival times. In multivariate analysis, LC3B expression remained an independent prognostic factor (p = 0.025) for overall survival. In conclusion, autophagy may play a role in the tumorigenesis of SIACs, and LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for SIACs.

Comment on Jun, S.Y.; et al. “Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma” Cancers 2020, 12, 2199

We read with interest the paper by Jun S [...]

Reply to Comment on “Jun, S.Y.; et al. Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma” Cancers 2020, 12, 2199

We thank Giuffrida et al [...]

Prognostic implication of SOX2 expression in small intestinal adenocarcinoma

Background: The presence of KRAS mutation enhance the stem cell features of colorectal carcinoma cells containing mutant adenomatous polyposis coli (APC). However, their potential role in small intestinal adenocarcinoma remains elusive. Here, we aimed to investigate the clinical significance of cancer stem cell markers in the context of small intestinal adenocarcinoma with the KRAS genotype. Methods: SOX2, NANOG, and OCT4 expression were assessed by immunohistochemistry and digital image analysis, and their potential association with KRAS was further examined in 185 small intestinal adenocarcinoma patients. Results: Positive expression of SOX2, NANOG, and OCT4 was detected in 65 (35.1%), 94 (50.8%), and 82 (44.3%) of patients, respectively. SOX2-/wild-type KRAS (KRASWT) was often observed in low-grade carcinoma (P = 0.048). SOX2+ and SOX2+/mutant KRAS (KRASMT) were significantly associated with shorter overall survival relative to SOX2- and others (P < 0.001, both). Multivariate analysis revealed SOX2+ (HR=1.929 [95% CI, 1.320-2.819], P = 0.001) as an independent prognostic factor of worse overall survival among small intestinal adenocarcinoma patients. Conclusions: These results suggest that SOX2 expression, in conjunction with KRAS, is a potential prognostic marker for small intestinal adenocarcinoma.