1.MLH1 promoter hypermethylation predicts poorer prognosis in mismatch repair deficiency endometrial carcinomas
Enami KANEKO ; Naoki SATO ; Tae SUGAWARA ; Aya NOTO ; Kazue TAKAHASHI ; Kenichi MAKINO ; Yukihiro TERADA
Journal of Gynecologic Oncology 2021;32(6):e79-
Objective:
The antitumor effects of anti-PD-1 antibody against mismatch repair deficiency (MMR-D)-associated cancers have been reported. MMR-D is found in approximately 20%–30% of endometrial carcinomas (ECs) and frequently occurs due to MLH1 promoter hypermethylation (MLH1-PHM). ECs with MLH1-PHM are classified according to the molecular screening of Lynch syndrome (LS), but few detailed reports are available. The purpose of this study was to clarify the clinical features of EC with MLH1-PHM.
Methods:
Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed on specimens from 527 ECs treated at our university hospital from 2003 to 2018. MLH1 methylation analysis was added to cases with MLH1/PMS2 loss. ECs were classified as follows: cases that retained MMR proteins as “MMR-proficient;” cases with MLH1/PMS2 loss and MLH1-PHM as “met-EC;” and cases with other MMR protein loss and MLH1/PMS2 loss without MLH1-PHM as “suspected-LS.” The clinical features, including long-term prognosis, of each group, were analyzed.
Results:
Accordingly, 419 (79.5%), 65 (12.3%), and 43 (8.2%) cases were categorized as “MMR-proficient,” “suspected-LS,” and “met-EC,” respectively. Significantly, “met-EC” had a lower proportion of grade 1 tumors (37.5%) and a higher proportion of stage III/IV tumors (37.2%) than the other groups. The overall and progression-free survival of “met-EC” were significantly worse than those of “suspected-LS” in all cases.
Conclusion
In ECs with MMR-D, “met-ECs” were a subgroup with a poorer prognosis than “suspected-LS.” “Met-ECs” would be the main target for anti-PD-1 antibody treatment, and its clinical susceptibility should be verified individually.
2.Activities of the Ishikawa Prefectural Joint Committee of Blood Transfusion Therapy
Naohiro SUGITA ; Hiroshi TANAKA ; Hidehiro SATOU ; Tosihiko HUTAKI ; Makiko MIYAMOTO ; Sinitiro YONEDA ; Aya OKAMOTO ; Yo TANIGUCHI ; Ikue YAMASITA ; Makoto NITTA ; Masaki KOMORI ; Shintaro SHIOBARA ; Shuichi KIKUCHI ; Akiyoshi TAKAMI ; Hirohito YAMAZAKI ; Yasufumi MASAKI
Japanese Journal of Social Pharmacy 2018;37(1):2-8
Objective : In 2011, the Ishikawa Prefectural Joint Committee of Blood Transfusion Therapy was organized in Ishikawa Prefecture. Since 2012, pharmacists have promoted educational activities regarding the appropriate use of albumin products for different occupations based on a survey involving all medical institutions in Ishikawa Prefecture. We examined the effects of these activities with respect to the usage of albumin products. Methods : A questionnaire survey regarding blood transfusion therapy, including the total usage of albumin products, departments responsible for the management of albumin products, and health care professionals’ awareness of issues on the appropriate use of albumin products, was conducted from 2011 until 2014 involving all medical institutions where blood transfusion preparations were used in Ishikawa Prefecture. Results : The questionnaire collection rate was ≥70%. The results showed that, in middle- or small-scale medical institutions, departments/physicians other than the Department of Pharmacy were responsible for the management of albumin products. Furthermore, some health care professionals did not recognize/understand problems regarding the appropriate use of albumin products. Pharmacists newly increased educational activities by study meetings for various occupations or panel discussions involving participants. The participants’ occupations varied, and the number of institutions to which they belonged was 20 to 24. The total usage of albumin products in Ishikawa Prefecture decreased by approximately 20% between 2011, when these attempts were started, and 2014. Discussion : This study suggests that the educational activities by pharmacists and other health care professionals at the prefectural level reduced the total usage of albumin products.