Mismatch repair proteins expression and tumor-infiltrating T-cells in colorectal cancer.

Microsatellite instability (MSI) and tumor mutational burden (TMB) are indicators of the tumor mutational load, which can lead to immune cell recruitment. By contrast, the number of tumor-infiltrating T cells (TITs) is indicative of the host immune response to tumor cells. The present study evaluated if the expression of mismatch repair (MMR) proteins can be used as a precise tool to assess immunogenicity in the tumor microenvironment. A total of 73 colorectal cancer cases were enrolled in the present study. MMR protein expression was assessed using four-antibodies immunohistochemistry (IHC) targeting MLH1, MSH2, MSH6 and PMS2. TIT was assessed through IHC by counting CD3+ and CD8+ cells in tumor. The enrolled cases were classified into four groups according to MMR and TIT status i) Mismatch repair-proficient (pMMR) and a high number of TITs (pMMR/TIT-H); ii) pMMR and a low number of TITs (pMMR/TIT-L); iii) mismatch repair-deficient (dMMR) and TIT-H (dMMR/TIT-H); and iv) dMMR/TIT-L]. The present study evaluated the clinicopathological characteristics of the four groups, in addition to the difference of TMB. TMB analysis was counted the number of the somatic mutations through multi-genes panel using next-generation sequencing. Clinicopathological characteristics, including age, sex, pathological depth of invasion and lymph node metastasis, were not found to be statistically different between dMMR/TIT-H and dMMR/TIT-L groups. Tumors among pMMR/TIT-H group were associated with poorly differentiation compared with those in pMMR/TIT-L group (P=0.025). The median TMB among the dMMR/TIT-H group was the highest in four groups but the median TMB was <10 muts/Mb in dMMR/TIT-L, pMMR/TIT-H and pMMR/TIT-L groups, respectively. However, one tumor in the pMMR/TIT-H group showed high TMB. The present findings suggest that assessing MMR status alone may not be sufficient to precisely evaluate the antitumor immune response in the tumor microenvironment.

[A Case of Solitary Liver Metastasis of Low-Grade Endometrial Stromal Sarcoma 31 Years after Resection of Primary Lesion].

A 73-year-old woman was referred to our hospital after a liver tumor was discovered during an abdominal ultrasonography. Thirty-one years ago, she underwent a total hysterectomy for uterine myoma and was diagnosed with a leiomyoma. Twenty years ago, she underwent a bilateral oophorectomy for an ovarian tumor and was diagnosed with a luteinized theca cell tumor accompanied by sclerosing peritonitis. A CT scan and MRI revealed a 65-mm tumor in the S6-7 of the liver. There was no sign of any lesions other than in the liver, and TACE was performed for suspected hepatocellular carcinoma. However, a favorable treatment outcome was unable to be obtained and a posthepatic segmental resection was performed. Histopathological morphology suggested a similarity to endometrial stromal cells and, considering the history of myoma of the uterus and ovarian tumor, immunohistological staining was carried out. The myoma of the uterus and the ovarian and liver tumors were all CD10(+), α⊖SMA(-), MIB-1 index 3%. The uterine myoma, which was initially operated on, was rediagnosed as a low-grade endometrial stromal sarcoma. After 11 years, ovarian metastasis was observed, and after 31 years liver metastasis occurred. Examples of resection of liver metastasis of endometrial stromal sarcoma are extremely rare and, we will include a review of the literature in this report.

Investigation of clinicopathological characters and gene expression features in colorectal signet-ring cell carcinoma utilizing CMS classification.

Signet ring cell carcinoma (SRCC) is a rare pathological type of colorectal cancer, of which the clinicopathological features and genetic background have not yet been fully investigated. Previous research has focused on the optimization of colorectal cancer treatment utilizing consensus molecular subtyping (CMS). However, it is not known what type of CMS would be designated to SRCC treatment. In the current study, of 1,350 patients diagnosed with colorectal cancer who underwent surgery, 14 were diagnosed with SRCC. The case-control cohort that fit the clinical background of the SRCC case was constructed. Statistical comparison between the SRCC group and the case-control cohort was performed among clinicopathological variables. SRCC and well to moderately adenocarcinoma case mRNA were submitted to microarray analysis and CMS analysis. Compared with the case-control cohort, the SRCC group was located more in the right-sided colon, the lymphatic invasion was more severe and the peritoneal dissemination was more frequent. The cancer-specific survival and the progression-free survival were significantly worse in the SRCC group compared with the case-control cohort. Microarray and CMS analysis identified that one SRCC case was significantly well assigned in the CMS 4 group and the other case was assigned in the CMS 1 group. Gene set analysis revealed the upregulation of EMT related genes and the downregulation of fatty acid, glycolysis, differentiation, MYC, HNF4A, DNA repair genes. In conclusion, the clinical characteristics of SRCC are severe but there is a possibility of the presence of different phenotypes according to CMS analysis.

Mesocolic hernia following retroperitoneal laparoscopic radical nephrectomy: A case report.

INTRODUCTION: Small bowel obstruction (SBO) caused by an internal hernia through a mesocolon after retroperitoneal laparoscopic nephrectomy (RLN) is rare. PRESENTATION OF CASE: A 66-year-old man who had undergone RLN with bladder cuff excision for a left renal pelvic cancer. After the surgery, he experienced SBO repeatedly. Contrast-enhanced computed tomography (CT) and gastrografin contract radiography through a long tube showed an internal hernia through the mesocolon to the retroperitoneal space where the resected left kidney had been located. We performed a subsequent surgery for the internal hernia. Postoperative course was uneventful and currently he has no recurrence of herniation 6 months post-operatively. DISCUSSION: Mesenteric defects that cause an internal hernia can be created inadvertently during RLN when the colon is mobilized medially, and the kidney is being detached from retroperitoneum. The removal of a kidney leads to a potential retroperitoneal space to which small intestine can migrate. While there is no absolute necessity in mobilizing the colon during the retroperitoneal laparoscopic approach, there is still a risk of making mesocolic defects directly in the retroperitoneal space. CONCLUSION: We need to perform operations with sufficient anatomical knowledge of retroperitoneal fascia and careful surgical techniques. The critical thing to prevent an internal hernia following RLN is to close the mesenteric defects intraoperatively. It is also important to suspect an internal hernia and do proper examinations promptly when patients had the symptoms of SBO after nephrectomy.

Correction to: The Immunoscore is a Superior Prognostic Tool in Stages II and III Colorectal Cancer and is Significantly Correlated with Programmed Death-Ligand 1 (PD-L1) Expression on Tumor-Infiltrating Mononuclear Cells.

In the original article, Akihiko Kawahara's first name is incorrect. It is correct as reflected here.

The Immunoscore is a Superior Prognostic Tool in Stages II and III Colorectal Cancer and is Significantly Correlated with Programmed Death-Ligand 1 (PD-L1) Expression on Tumor-Infiltrating Mononuclear Cells.

BACKGROUND: In colorectal cancer (CRC), the indication for immune checkpoint inhibitors is determined by the microsatellite instability status of the tumors. However, an optimal biomarker for their indication has not been fully identified to date. This study aimed to establish the clinicopathologic importance of the Immunoscore (IS) in CRC and to clarify the relationships between the IS, programmed death-ligand 1 (PD-L1) expression, and tumor-associated macrophages. METHODS: In 132 cases, CRC was diagnosed and surgically treated in our department from 2009 to 2010. Immunohistochemical staining using primary antibodies PD-L1, CD3, CD8, CD68, and CD163 was performed. The IS was determined according to the proposal of an international task force. Statistical analyses were performed to investigate the correlation between the IS, clinicopathologic variables, and expression of immune checkpoint molecules. RESULTS: The overall survival (OS) and relapse-free survival (RFS) in the high-IS group (I3-4) were significantly better than in the low-IS group (I0-2) (OS: P = 0.0420; RFS: P = 0.0226). The positivity rate for PD-L1 on tumor cells (tPD-L1) was only 0.8%, whereas that for PD-L1 on interstitial tumor-infiltrating mononuclear cells (iPD-L1) was 18.2%. The iPD-L1-positive group showed significantly better survival in terms of both OS and RFS than the iPD-L1-negative group (OS: P = 0.0278; RFS: P = 0.0253). The findings showed significant correlation between the IS and iPD-L1 expression (P < 0.0001). CONCLUSIONS: The study found that a high IS was a good indicator of a better prognosis and significantly correlated with iPD-L1 expression in CRC.