TY - JOUR
T1 - Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma
AU - yasutake, nobuko
AU - Iwasaki, Takeshi
AU - Yamamoto, Hidetaka
AU - Sonoda, Kenzo
AU - Kodama, Keisuke
AU - Kaoru, Okugawa
AU - Asanoma, Kazuo
AU - Yahata, Hideaki
AU - Kato, Kiyoko
AU - Oda, Yoshinao
N1 - Funding Information:
The authors thank K. Taguchi (National Kyushu Cancer Centre, Fukuoka), Y. Hiraki, Y. Ohishi and M. Oya (Aso Iizuka Hospital, Fukuoka), Y. Oshiro (Japanese Red Cross Matsuyama Hospital, Ehime), M. Mine (Kyushu Central Hospital, Fukuoka), Y. Nakashima, K. Nishiyama and M. Nishida (Japanese Red Cross Fukuoka Hospital, Fukuoka), J. Motoshita and Y. Ueoka (Hamanomachi Hospital, Fukuoka), Y. Yoshikawa and H. Sumioki (Beppu Medical Centre, Oita), S. Kato and K. Sakai (Saiseikai Fukuoka General Hospital, Fukuoka) for providing clinical histological data. This work was supported by a Grand-in-Aid for Scientific Research (19H03444, 17K11281 and 21K20805). The authors would like to thank Enago (www.enago.jp) for the English language review. JSPS KAKENHI Grant/Award Numbers: 19H03444, 17K11281 and 21K20805. NY contributed to the study design, reviewed the slides, analysed the data and wrote the manuscript. TI contributed to the study design, reviewed the slides, analysed the data and finalised the manuscript. HY helped with immunohistochemistry and read the manuscript. KS and KK helped with immunohistochemistry. KO, KA, HY and KK finalised the manuscript. YO contributed to the study design. All authors have read and approved the final manuscript. The authors have no potential conflicts of interest to disclose.
Funding Information:
The authors thank K. Taguchi (National Kyushu Cancer Centre, Fukuoka), Y. Hiraki, Y. Ohishi and M. Oya (Aso Iizuka Hospital, Fukuoka), Y. Oshiro (Japanese Red Cross Matsuyama Hospital, Ehime), M. Mine (Kyushu Central Hospital, Fukuoka), Y. Nakashima, K. Nishiyama and M. Nishida (Japanese Red Cross Fukuoka Hospital, Fukuoka), J. Motoshita and Y. Ueoka (Hamanomachi Hospital, Fukuoka), Y. Yoshikawa and H. Sumioki (Beppu Medical Centre, Oita), S. Kato and K. Sakai (Saiseikai Fukuoka General Hospital, Fukuoka) for providing clinical histological data. This work was supported by a Grand-in-Aid for Scientific Research (19H03444, 17K11281 and 21K20805). The authors would like to thank Enago (www.enago.jp) for the English language review.
Publisher Copyright:
© 2022
PY - 2022/7
Y1 - 2022/7
N2 - Cyclin-dependent kinase 8 (CDK8) is associated with the transcriptional mediator complex and regulates several transcription factors implicated in cancer. CDK8 expression is a poor prognostic marker in colon and breast cancer by immunohistochemistry. However, somatic mutations in exon 2 of the RNA polymerase II transcriptional mediator subunit MED12 occur in 7–30% of cases of uterine leiomyosarcoma (ULMS), suggesting that these alterations contribute to tumorigenesis. Public genomic mutation data of 80 patients with ULMS were used for MED12 and CDK8 mutation analysis. The expression of MED12, CDK8 and β-catenin was evaluated by immunohistochemistry in our cohort of 60 patients with ULMS, in addition with MED12 mutation status and survival stage. Univariate analysis was performed using the log-rank test, and Cox regression was used to identify independent prognostic factors. Multivariate Cox regression analysis revealed that advanced stage (p < 0.0001) and high CDK8 expression (p = 0.0014) were independent predictors of poor prognosis. MED12 mutation status was not significantly associated with CDK8 expression (p = 0.6873) and DSS (p = 0.8075). In conclusion, our data suggest that CDK8 expression may identify a subset of ULMS patients with a poor prognosis.
AB - Cyclin-dependent kinase 8 (CDK8) is associated with the transcriptional mediator complex and regulates several transcription factors implicated in cancer. CDK8 expression is a poor prognostic marker in colon and breast cancer by immunohistochemistry. However, somatic mutations in exon 2 of the RNA polymerase II transcriptional mediator subunit MED12 occur in 7–30% of cases of uterine leiomyosarcoma (ULMS), suggesting that these alterations contribute to tumorigenesis. Public genomic mutation data of 80 patients with ULMS were used for MED12 and CDK8 mutation analysis. The expression of MED12, CDK8 and β-catenin was evaluated by immunohistochemistry in our cohort of 60 patients with ULMS, in addition with MED12 mutation status and survival stage. Univariate analysis was performed using the log-rank test, and Cox regression was used to identify independent prognostic factors. Multivariate Cox regression analysis revealed that advanced stage (p < 0.0001) and high CDK8 expression (p = 0.0014) were independent predictors of poor prognosis. MED12 mutation status was not significantly associated with CDK8 expression (p = 0.6873) and DSS (p = 0.8075). In conclusion, our data suggest that CDK8 expression may identify a subset of ULMS patients with a poor prognosis.
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U2 - 10.1016/j.prp.2022.153920
DO - 10.1016/j.prp.2022.153920
M3 - Article
C2 - 35605413
AN - SCOPUS:85130791982
SN - 0344-0338
VL - 235
JO - Pathology Research and Practice
JF - Pathology Research and Practice
M1 - 153920
ER -
