Immune checkpoint inhibitors with chemotherapy for primary advanced mismatch repair-deficient endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.

Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.

Application of preoperative fluorodeoxyglucose-PET/CT parameters for predicting prognosis of high-grade neuroendocrine cervical cancer.

OBJECTIVE: High-grade neuroendocrine cervical cancer (HGNECC) is a rare and aggressive cervical cancer subtype. In this study, we aimed to evaluate the prognostic value of fluorodeoxyglucose-PET/computed tomography (CT) parameters for HGNECC. MATERIALS AND METHODS: This single-center retrospective study included 29 patients with HGNECC who underwent fluorodeoxyglucose-PET/CT scan followed by surgery between 2006 and 2016. RESULTS: The median follow-up period was 40 (range, 4-184) months. After surgery, the resection margins were tumor-negative in 28 patients (96.6%), 8 (27.6%) patients had parametrial tumor invasion, and 7 patients (24.1%) tested positive for lymph node metastasis. The tumor recurred in 20 patients (69%) and 18 patients (62.1%) died during the observation period. In the univariate analyses, age and total lesion glycolysis (TLG) were associated with worse disease-free survival (DFS) (age, hazard ratio 1.056, 95% CI 1.014-1.100, P  = 0.009; TLG2.5, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.033; and TLG3.0, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.034). In the multivariate analyses, older age and higher TLG3.0 were identified as independent poor prognostic factors for DFS (age, hazard ratio 1.058, 95% CI 1.014-1.104, P  = 0.009; TLG3.0, hazard ratio 1.004, 95% CI 1-1.007, P  = 0.033), while resection margin involvement was identified as an independent factor to predict poor overall survival (hazard ratio 20.717, 95% CI 1.289-332.964, P  = 0.032). CONCLUSION: Among the preoperative fluorodeoxyglucose-PET/CT parameters, TLG3.0 may be useful for predicting DFS in patients with HGNECC.

Outcomes and prognostic factors of surgically treated extramammary Paget's disease of the vulva.

OBJECTIVE: Extramammary Paget's disease (EMPD) of the vulva is a rare disease which predominantly presents in postmenopausal Caucasian women. As yet, no studies on Asian female patients with EMPD have been performed. This study aimed to identify the clinical features of patients with vulvar EMPD in Korea, and to evaluate the risk factors of recurrence and postoperative complications in surgically treated EMPD. METHODS: We retrospectively reviewed 47 patients with vulvar EMPD who underwent wide local excision or radical vulvectomy. The clinical data and surgical and oncological outcomes following surgery were extracted from medical records and analyzed. Univariate and multivariate analyses for predicting recurrence and postoperative complications were performed. RESULTS: 21.3% of patients had complications after surgery, and wound dehiscence was the most common. 14.9% of patients experienced recurrence, and the median interval to recurrence from initial treatment was 69 (range 33-169) months. Vulvar lesions larger than 40 mm was the independent risk factor of postoperative complications (odds ratio [OR]=7.259; 95% confidence interval [CI]=1.545-34.100; p=0.012). Surgical margin status was not associated with recurrence in surgically treated vulvar EMPD patients (OR=0.83; 95% CI=0.16-4.19; p=1.000). CONCLUSION: Positive surgical margin is a frequent finding in the patients with vulvar EMPD, but disease recurrence is not related with surgical margin status. Since EMPD is a slow growing tumor, a surveillance period longer than 5 years is required.

Single-Incision versus Multiport Robotic Myomectomy: A Propensity Score Matched Analysis of Surgical Outcomes and Surgical Tips.

We aimed to compare the perioperative outcomes of single-incision robotic myomectomy (SIRM) and multiport robotic myomectomy (MPRM) and provide surgical tips. We retrospectively analyzed the medical records of 462 patients with symptomatic leiomyoma who underwent MPRM or SIRM between March 2019 and April 2021. Demographic characteristics and surgical outcomes, including the total operative time (OT), estimated blood loss (EBL), and surgical complication rate, were compared between the two groups. Patients in the SIRM group had lower a body mass index and rate of previous pelvic surgery and were younger than those in the MPRM group. The myoma type was not different between groups; however, the MPRM group had larger, and more myomas than the SIRM group. After propensity score matching, these variables were not significantly different between the groups. The total OT, EBL, difference in hemoglobin levels, transfusion rate, and postoperative fever were not different between the groups. No postoperative complications occurred in the SIRM group. In the MPRM group, one patient needed conversion to laparotomy, and two patients had postoperative complications (umbilical incisional hernia and acute kidney injury). In conclusion, both MPRM and SIRM are feasible and effective surgical options for symptomatic myomas with cosmetic benefits and minimal risk of laparotomy conversion.

The Clinical Significance and Utility of HPV-DNA Testing in Korean Women with Atypical Glandular Cells in Cervical Pap Tests: An Analysis of 311 Cases at a Single Institution.

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1 vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.

Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer.

PURPOSE: The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. METHODS: We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. RESULTS: All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. CONCLUSION: Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.

Development of Machine Learning Models to Predict Platinum Sensitivity of High-Grade Serous Ovarian Carcinoma.

To support the implementation of individualized disease management, we aimed to develop machine learning models predicting platinum sensitivity in patients with high-grade serous ovarian carcinoma (HGSOC). We reviewed the medical records of 1002 eligible patients. Patients' clinicopathologic characteristics, surgical findings, details of chemotherapy, treatment response, and survival outcomes were collected. Using the stepwise selection method, based on the area under the receiver operating characteristic curve (AUC) values, six variables associated with platinum sensitivity were selected: age, initial serum CA-125 levels, neoadjuvant chemotherapy, pelvic lymph node status, involvement of pelvic tissue other than the uterus and tubes, and involvement of the small bowel and mesentery. Based on these variables, predictive models were constructed using four machine learning algorithms, logistic regression (LR), random forest, support vector machine, and deep neural network; the model performance was evaluated with the five-fold cross-validation method. The LR-based model performed best at identifying platinum-resistant cases with an AUC of 0.741. Adding the FIGO stage and residual tumor size after debulking surgery did not improve model performance. Based on the six-variable LR model, we also developed a web-based nomogram. The presented models may be useful in clinical practice and research.

New Surgical Technique for Robotic Myomectomy: Continuous Locking Suture on Myoma (LSOM) Technique.

Robot-assisted laparoscopic myomectomy (RALM) has broadened the indications even in complex myomas. However, the high cost of RALM remains the main disadvantage. Therefore, a surgical technique that can reduce the cost of RALM and still has the advantages of robotic surgery is required. We propose a "locking suture on myoma (LSOM)" technique and compared the operative and perioperative outcomes of patients who underwent RALM with or without the LSOM technique. We included 337 patients who underwent RALM with (n = 160) or without (n = 177) the LSOM technique between March 2019 and August 2020. The LSOM group had low parity and gravidity, with a low rate of Cesarean sections. Myoma type was not different between the groups; however, patients in the LSOM group had larger, heavier, and higher number of myomas, although fewer patients had multiple myomas and were discharged earlier. Total operating time, estimated blood loss, pre- and postoperative hemoglobin levels, transfusion rate, and postoperative fever were not different between the two groups. In conclusion, the LSOM technique may be a viable surgical option for myomas, as it can reduce the cost of RALM by obviating the need for robotic Tenaculum forceps.

Usefulness of sentinel lymph node mapping using indocyanine green and fluorescent imaging in the diagnosis of lymph node metastasis in endometrial cancer.

The lymph node status is the most important prognostic factor for endometrial cancer. This study aimed to assess whether sentinel lymph node mapping (SLNM) is applicable in endometrial cancer. A retrospective review of patients with endometrial cancer who were diagnosed and treated in Asan Medical Centre from September 2015 to December 2017 was conducted. One hundred patients underwent robotic (da Vinci®) or laparoscopic surgical treatment, including SLNM with indocyanine green (ICG) fluorescence detection using the Firefly® and NIR/ICG systems. At least one lymph node area was observed in 100% of SLNM cases. Sentinel node detection and frozen biopsy were performed in all cases, and all patients with metastasis were found on SLNM. The sensitivity and negative predictive value were both 100% in the patient-by-patient and station-by-station analyses. SLNM appears to be a feasible method to reduce the morbidity and increase the detection rate in early-stage endometrial carcinoma.What is already known on this subject? There are studies that it is safe to diagnose the possibility of lymph node metastasis through sentinel lymph node mapping in endometrial cancer.What do the results of this study add? In this study, it is shown that the accuracy of sentinel lymph node mapping is 100% accurate.What are the implications of these findings for clinical practise and/or further research? Therefore, total lymphadenectomy will not be necessary for the future.

Continued medical treatment for persistent early endometrial cancer in young women.

OBJECTIVE: We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients. METHODS: We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed. RESULTS: Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p < 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001). CONCLUSIONS: Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.

Robot-Assisted Laparoscopic Myomectomy versus Abdominal Myomectomy for Large Myomas Sized over 10 cm or Weighing 250 g.

PURPOSE: Here, we compared the operative and perioperative outcomes between robot-assisted laparoscopic myomectomy (RALM) and abdominal myomectomy (AM) in patients with large (>10 cm) or heavy myomas (>250 g). MATERIALS AND METHODS: We included 278 patients who underwent multi-port RALM (n=126) or AM (n=151) for large or heavy myomas in a tertiary care hospital between April 2019 and June 2020. The t-test, chi-square, Bonferroni's test, and multiple linear regression were used. RESULTS: No differences were observed in age, body mass index, parity, or history of pelvic surgery between the two groups. Myoma diameters were not different (10.8±2.52 cm vs. 11.2±3.0 cm, p=0.233), but myomas were lighter in the RALM group than in the AM group (444.6±283.14 g vs. 604.68±368.35 g, respectively, p=0.001). The RALM group had a higher proportion of subserosal myomas, fewer myomas, fewer large myomas over >3 cm, lighter myomas, and longer total operating time. However, the RALM group also had shorter hospital stay and fewer short-term complications. Estimated blood loss (EBL) was not different between the two groups. The number of removed myomas was the most significant factor (coefficient=10.89, p<0.0001) affecting the EBL. CONCLUSION: RALM is a feasible myomectomy technique even for large or heavy myomas. RALM patients tend to have shorter hospital stays and fewer postoperative fevers within 48 hours. However, RALM has longer total operating time.

An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2.

Recent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic heterozygous missense mutation (c.402C>G; p.C134W) in FOXL2, a feature shared by virtually all adult-type granulosa cell tumors (AGCTs), introduces a target site for miR-1236, which causes haploinsufficiency of the tumor-suppressor FOXL2. This miR-1236-mediated selective degradation of the variant FOXL2 mRNA is preferentially conducted by a distinct miRNA-loaded RNA-induced silencing complex (miRISC) directed by the Argonaute3 (AGO3) and DHX9 proteins. In both patients and a mouse model of AGCT, abundance of the inversely regulated variant FOXL2 with miR-1236 levels is highly correlated with malignant features of AGCT. Our study provides a molecular basis for understanding the conserved FOXL2 CDS mutation-mediated etiology of AGCT, revealing the existence of a previously unidentified mechanism of miRNA-targeting disease-associated mutations in the CDS by forming a non-canonical miRISC.

Feasibility and safety of fertility-sparing surgery in epithelial ovarian cancer with dense adhesion: a long-term result from a single institution.

OBJECTIVE: We investigated the feasibility and safety of fertility-sparing surgery (FSS) in patients with epithelial ovarian cancer (EOC) with dense adhesions. METHODS: Patients were divided into cases with and without dense adhesions in this retrospective study. RESULTS: Of the 95 eligible patients, 29 patients had dense adhesions. Mean age, proportion of staging procedure, distribution of histologic type, and co-presence of endometriosis were different (p=0.003, 0.033, 0.011, and 0.011, respectively). The median follow-up period was 57.8 (0.4-230.0) months. There were no differences in the rates of recurrence (21.2% vs. 20.7%, p=1.000) or death (16.7% vs. 6.9%, p=0.332) between the 2 groups. There was no difference in the pattern of recurrence or in disease-free survival (DFS) and overall survival (OS) between the 2 groups. In multivariate analysis, pretreatment cancer antigen-125 >35 U/mL and International Federation of Gynecology and Obstetrics stage IC were significant factors of worse DFS and OS, while dense adhesion was not a prognostic factor for both DFS (hazard ratio [HR]=0.9; 95% confidence interval [CI]=0.3-2.7; p=0.792) and OS (HR=0.2; 95% CI=0.1-1.8; p=0.142), nor were age, proportion of staging procedure, histologic type, and co-presence of endometriosis. Moreover, the distribution of those 2 significant prognostic factors was not different between the 2 groups. Dense adhesions were subgrouped into non-tumor and tumor associated dense adhesions for further analysis and the results were same. CONCLUSION: FSS is feasible and safe in EOC, regardless of the presence of dense adhesions.

Low value of staging in detecting extraovarian occult metastasis in mucinous borderline ovarian tumors.

OBJECTIVES: Staging procedure in borderline ovarian tumors is a topic of controversy. Upstaging in non-serous borderline ovarian tumors that are confined to the ovary is rare. The aim of this study was to assess the impact of surgical staging on clinical outcomes in mucinous borderline ovarian tumors. METHODS: This was a retrospective study conducted at the Asan Medical Center, Seoul, Korea between January 1990 and December 2015, that included 432 patients with mucinous borderline ovarian tumors and at least 6 months follow-up. These patients were divided into a 'staging group' and 'unstaged group'. The staging group referred to patients who, in addition to hysterectomy and/or adnexal surgery, underwent at least one of the following: cytology, omental biopsy/omentectomy, peritoneal biopsy, lymph node biopsy/lymphadenectomy, or appendectomy. The unstaged group referred to patients who did not undergo any staging procedure but underwent adnexal surgery (cystectomy or oophorectomy). RESULTS: Median patient age was 40 (range 9-87) years. A total of 367 patients (85%) underwent a staging procedure (staging group) and 65 (15.0%) patients did not (unstaged group). Among the staging group, 258, 4, 100, and 5 patients were FIGO stage IA, IB, IC, or II-III, respectively. Overall recurrence was confirmed in 15 patients and median time to recurrence was 13.4 (range 0.4-127.3) months. One patient was in the unstaged group and had borderline recurrence. Fourteen were in the staging group, and 11 of them had borderline and three had invasive recurrence. Extraovarian disease was found at recurrence only in two patients. There was no significant difference in recurrence-free survival (p=0.39) and in overall survival between the staging group and the unstaged group (p=0.40). In total, 16 (4.4%) of 367 patients who underwent a staging procedure were upstaged. CONCLUSION: Staging in mucinous borderline ovarian tumors may be omitted if there is no obvious evidence of gross extraovarian disease.

Prognostic Factors and Impact of Minimally Invasive Surgery in Early-stage Neuroendocrine Carcinoma of the Cervix.

STUDY OBJECTIVE: To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). DESIGN: Retrospective cohort study. SETTING: Asan Medical Center, Seoul, Korea. PATIENTS: Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. INTERVENTIONS: All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. MEASUREMENTS AND MAIN RESULTS: Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1-42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018-4.871; p =.045 and HR, 6.494; 95% CI, 1.415-29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188-8.815; p =.022 and HR, 12.710; 95% CI, 1.128-143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). CONCLUSION: Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.

BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells.

The adaptor-related protein complex 5 subunit mu 1 (AP5M1) is an evolutionally conserved protein with ubiquitous expression in human tissues. However, the major function of AP5M1 in living organisms is unclear owing to few published studies. Here, we demonstrate that AP5M1 is a potent apoptosis-inducing molecule in cervical cancer cells. We also found that AP5M1 upregulated the level of BAX protein, a key pro-apoptotic B cell lymphoma (BCL)-2 family member regulating mitochondrial apoptotic cell death pathway. Moreover, AP5M1 completely lost its apoptotic activity in BAX-knockout or -knockdown cells, indicative of its functional dependence on BAX. Comparative analysis of cervical tissues from patients with cervical carcinoma and non-cancer control revealed a prominent downregulation in AP5M1 expression with a concomitant downregulation in BAX expression; AP5M1 and BAX mRNA expression levels in cervical tissues exhibited a strong positive correlation (r = 0.97). Thus, we identified AP5M1 as a previously unrecognized apoptotic protein that governs BAX expression and revealed the association between AP5M1 and malignancy.

The combination of histone deacetylase and p53 expressions and histological subtype has prognostic implication in uterine leiomyosarcoma.

OBJECTIVE: To investigate the expression of different histone deacetylases and their association with disease characteristics and survival outcomes in uterine leiomyosarcoma patients. METHODS: The immunohistochemical expression of different histone deacetylases and p53 by tissue microarray and histological subtypes were assessed in tumor tissue samples of 42 eligible patients. RESULTS: Histone deacetylases 1-4, 6 and 8 showed prevalent and strong (3+) expression (88.1, 90.5, 95.2, 92.9, 83.3 and 100%, respectively). Histone deacetylases 5, 7 and 9 showed infrequent strong expression (33.3, 50 and 38.1%, respectively). There were trends of higher disease-free survival rates according to the combination of weaker expression of histone deacetylase 5, 7 or 9 with positive p53 expression or with non-epithelial subtype. The patients with triple-positive favorable prognostic factors (any of weaker histone deacetylase 5, 7 and 9 expression, p53 positive, and non-epithelioid subtype) had the better survival outcomes while the patients with other combinations had the worse survival outcomes. In multivariate analysis, histone deacetylase 5 in combination with epithelioid subtype was an independent predictor for disease-free survival. CONCLUSIONS: Expression of histone deacetylase 5, 7 and 9 is a potential prognostic marker in uterine leiomyosarcoma when combined with pathologically relevant prognostic factors (p53 and histological subtype). This prevalent and strong histone deacetylase expression warrants further study in well-designed investigations of histone deacetylases as therapeutic targets in uterine leiomyosarcoma.