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Background and Aim: Pancreatic intraductal papillary mucinous neoplasm (IPMN) is one of the most common precancerous lesions of pancreatic carcinoma. Studies have found that the tumoral microbiome has an important influence on pancreatic carcinoma. However, the tumoral microbiome of IPMNs has rarely been explored. Methods: Tumoral microbiome gene sequencing was carried out using 16 specimens of IPMN and 45 specimens of IPMN with associated invasive carcinoma (IPMN‐IC) by 2bRAD sequencing for microbiome. The profile of the tumoral microbiome was summarized. Associations of the tumoral microbiome with disease grade, histological subtype, and prognosis were analyzed. Results: A total of 598 species of microbes were identified, comprising 228 genera, 109 families, 60 orders, 29 classes, 14 phyla, and 2 kingdoms. The genus Pseudomonas was detected more frequently and had higher relative abundance in IPMN‐ICs; Alcaligenes faecalis was detected with higher relative abundance in IPMNs. Bifidobacterium pseudolongum had a higher relative abundance in the IPMN‐IC group, regardless of histological subtype. Moreover, among patients with IPMN‐ICs, those with a high relative abundance of B. pseudolongum had better overall survival than those with a low relative abundance. Patients who were positive for Staphylococcus aureus or Mycolicibacillus koreensis had shorter survival. The presence of S. aureus was an independent risk factor for poor prognosis. Conclusions: There are enriching tumoral microbes in IPMN. The tumoral microbiome of IPMN is different from that of IPMN‐IC. [ABSTRACT FROM AUTHOR]

Objective: Immunohistochemistry is routinely performed to detect mismatch repair deficiency in solid tumors. Heterogeneous MMR expression (MMR-het) has been reported occasionally but not systemically studied., Methods: In this study, we depicted MMR-het patterns of 40 tumors of different anatomical sites and analyzed MMR genetic alterations and tumor mutational burdens (TMB) through comprehensive genomic profiling., Results: The MMR-het patterns were classified into 4 subgroups: "single-loss" (3 cases), "MLH1/PMS2 double-loss" (16 cases), "MSH2/MSH6 double-loss" (8 cases), and "triple/tetra-loss" (13 cases). Seventeen MMR-het cases exhibited histological heterogeneity, in which MMR protein loss was generally confined to either poorly differentiated or well-differentiated tumor areas. All "single-loss" tumors had MMR somatic mutations and coexisting POLE exonuclease domain mutations. "MLH1/PMS2 double-loss" tumors unexceptionally harbored MLH1 hypermethylation without MMR germline mutations. In the "MSH2/MSH6 double-loss" subgroup, 4 cases had MSH2/MSH6 germline mutations, while another 4 cases had multiple MSH2/MSH6 somatic mutations. Additional POLE exonuclease domain mutations were identified in 2 cases. Tumors in the "triple/tetra-loss" subgroup generally had MLH1 abnormalities (8 MLH1 hypermethylation, 4 MLH1 germline mutation, 1 MLH1 double somatic mutations), and coexistent somatic mutations on MSH2/MSH6 . Thirty-one cases (83.8%) were TMB-H, and all POLE -mutated cases exhibited ultra-high TMB (111.4 to 524.2 mut/Mb)., Conclusion: Our findings highlighted the importance of accurately interpreting heterogeneous MMR protein staining patterns for developing a more efficient personalized genetic investigation strategy., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The present study aimed to explore the clinicopathological characteristics, potential heterogeneity and prognostic factors in synchronous bilateral breast cancer (SBBC)., Methods: We performed a retrospective review and paired comparison of the clinicopathological characteristics of 114 patients with SBBC in the Peking Union Medical College Hospital from January 2008 to September 2019. The prognostic significance of triple negativity status and coexistence ductal carcinoma in situ (DCIS) with bilateral invasive ductal carcinomas of no special type (IDC-NST) was analyzed in SBBC., Results: Most bilateral lesions on both sides were of IDC-NST, grade 2, luminal subtype, and stage I. Although most lesions were concordant between the left and right side, discordances were observed in histological type (25 cases, 21.9%), histological grade (31 cases, 27.2%), pTNM (61 cases, 53.5%), molecular subtypes (20 cases, 17.5%), and immunohistochemical staining of ER (18 cases, 15.8%), PR (26 cases, 22.8%), and HER2 (12 cases, 10.5%). Moreover, there was no significant difference in disease-free survival (DFS) and overall survival (OS) between IDC-NST with coexisting DCIS on both sides and IDC-NST with coexisting DCIS on one side or pure IDC-NST. SBBC with triple negativity on both sides exhibited a significantly shorter DFS and OS when compared with triple negativity on one side or non-triple negativity on both sides (p<0.001), and remained an independent prognostic factor by multivariate analysis., Conclusions: A considerable proportion of discordance in clinicopathological characteristics is observed in SBBC, supporting the necessity of comprehensive pathological examination including immunohistochemical testing on both sides in clinical practice. Moreover, SBBC with triple negativity on both sides is a prognostic for poor survival., (©The Author(s) 2022. Open Access. This article is licensed under a Creative Commons CC-BY International License.)