The Kurume Medical Journal

Achievement of Surgical Proficiency in Laparoscopic Surgery for Early Endometrial Cancer by Gynecologic Oncologists

Although studies have evaluated learning curves for laparoscopic surgery (LS), this issue has not yet been addressed in gynecologic oncologists. The present study aimed to evaluate LS proficiency for early-stage endometrial cancer among gynecologic oncologists. We examined 25 cases in which LS with pelvic lymphadenectomy (PLA) for endometrial cancer was performed by two gynecologic oncologists undergoing training in LS. The LS duration, estimated blood loss (EBL), number of dissected pelvic lymph nodes (PLNs), and perioperative complications were assessed as measures of surgical proficiency. Operators A and B performed 10 and 15 cases, respectively, with median LS durations of 348.5 and 378 minutes, respectively. Although the LS duration and number of procedures did not exhibit a significant correlation, the regression lines for both operators showed decreasing trends. Both operators had a consistently low median EBL (A, 57 ml; B, 60 ml). Operators A and B dissected a median of 21.5 and 22 PLNs, respectively. Although both operators dissected a relatively large number of PLNs, with a median of over 20 per patient after the introduction of LS, this number decreased as the number of LS increased for Operator B (p=0.009). However, no correlation was observed between the LS duration and number of PLNs dissected by Operator B (ρ=0.353, p=0.197). A severe perioperative complication, specifically perforation of the sigmoid colon requiring emergent laparotomy, occurred in one case; however, the association with surgical manipulation was not definitive. The observed gynecologic oncologists were able to acquire early proficiency in LS for early-stage endometrial cancer.

N-Myc Downstream Regulated Gene-1 May Play an Important Role in the Prognosis of Ovarian Cancer, in Its Association with Beta-Catenin

NDRG1 is a nickel- and calcium-inducible gene that plays important roles in the primary growth of malignant tumors, as well as in invasion and metastasis. This study investigated the associations of NDRG1 expression with cell adhesion and other clinicopathological factors in ovarian cancer. The clinical records of 123 women who underwent surgery for ovarian cancer in our institute were reviewed retrospectively. The expression of NDRG1, E-cadherin, and beta-catenin in surgical specimens were evaluated immunohistochemically. The NDRG1 expression level was significantly associated with beta-catenin expression, peritoneal metastasis outside the pelvic cavity, lymph node metastasis, and FIGO stages. The Kaplan-Meier analysis showed a significant association between the NDRG1 expression level and progression-free survival: high NDRG1 expression was related to poor survival. Our results suggest that the increased expression of NDRG1 is associated with cell adhesion and may be a poor prognostic indicator in women with ovarian cancer.

Comprehensive Molecular Profiling and Clinicopathological Characteristics of Gastric-Type Mucinous Carcinoma of the Uterine Cervix in Japanese Women

Gastric-type mucinous carcinoma (GAS) of the uterine cervix is the most common adenocarcinoma that develops independently of human papillomavirus infection; it is typically diagnosed at an advanced stage and has a poorer prognosis than usual-type endocervical adenocarcinoma. Few studies have examined the molecular profile of GAS, but genetic alterations in TP53 and STK11 have been repeatedly reported. We analyzed the clinicopathological characteristics and molecular profile of GAS. Fresh-frozen tissue specimens and formalin-fixed paraffin-embedded (FFPE) tissues from 13 patients with GAS treated between January 2000 and December 2020 were analyzed. We performed next-generation sequencing on eight fresh-frozen GAS specimens using the Cancer Hotspot Panel v2 (cases 1-8) and the FoundationOne companion diagnostic (F1CDx) assay on six FFPE samples (cases 8-13). Seventy-four genomic alterations were identified in 42 genes. In order of frequency, TP53, ATRX, CDKN2A, KRAS, APC, and STK11 were altered in at least three cases. Targetable genomic alterations were identified in all six patients' specimens analyzed using the F1CDx assay. GAS harbors various genomic alterations associated with sustained activation of signaling pathways or cell cycle regulation in addition to abnormalities in TP53, and precision medicine based on molecular profiling will be necessary to overcome GAS.

High Expression of NDRG1 is a Poor Prognostic Factor in Patients with Endometrial Endometrioid Carcinoma with Long-Term Observation

N-myc downstream regulated gene-1 (NDRG1) has attracted much attention as a protein associated with angiogenesis. This study investigated the associations of NDRG1 expression, determined by immunohistochemical analysis, with other clinicopathological factors and prognosis in patients with endometrial endometrioid carcinoma (EEC). Surgical specimens were obtained from 113 patients with EEC. High NDRG1 expression was correlated with advanced stage, poor differentiation, lymph node metastasis, and significantly poorer survival compared with patients with low expression. High expression of NDRG1 was also correlated with high levels of angiogenesis and low expression of the estrogen receptor. These results suggest that high expression of NDRG1 is associated with angiogenesis and is an indicator of a poor prognosis in women with EEC.

Vulvar Adenoid Cystic Carcinoma with Squamous Cell Carcinoma Component

Adenoid cystic carcinoma (ACC) is a major histological type of salivary gland cancer but an uncommon form of vulvar cancer. Salivary gland ACC occasionally dedifferentiates into high-grade carcinoma, resulting in poor prognoses. The dedifferentiated component is usually a poorly differentiated cribriform or solid carcinoma, whereas squamous cell carcinoma (SCC) is exceptional. Herein, we report the case of a 78-year-old woman with vulvar ACC, including an SCC component. She presented with a vulvar nodule that had been present for 30 years and increased in size over the past few years. Magnetic resonance imaging showed a ball-like mass with high intensity on T1-weighted images and high intensity with non-uniformity on T2-weighted images. Considering the systemic and social conditions, the tumor was maximally resected without lymphadenectomy. Histologically, the tumor was composed of a marginal ACC component with a central SCC component. Stage IB vulvar cancer, which was assumed to originate from the Bartholin's gland, was diagnosed. She has survived over 2 years without additional treatments after the surgery. In this case, we assumed that slowly progressive indolent ACC could be dedifferentiated to high- grade SCC. According to our review of available literature, dedifferentiation of vulvar ACC with a high-grade SCC component has not been specifically documented. Although the nature of dedifferentiated vulvar cancer is unclear, it should be noted that high-grade dedifferentiation can occur in long-lasting vulvar masses.

Association of Chemotherapy Response Score with Multidrug Resistance 1 and CA125 ELIMination Rate Constant K in Patients with Advanced Ovarian Cancer Treated with Neoadjuvant Chemotherapy

The relationship between chemotherapy response score (CRS), a widely used response predictor of neoadjuvant chemotherapy-interval debulking surgery (NAC-IDS), and multidrug resistance 1 (MDR1) and CA125 ELIMination rate constant K (KELIM), is undetermined. We evaluated CRS in advanced ovarian cancer patients undergoing NAC and looked for associations between CRS and MDR1 and CA125 KELIM. Our aim was to predict the therapeutic effect of NAC before interval debulking surgery (IDS) by examining its association with CRS. This retrospective cohort study included patients who underwent NAC-IDS (first-line treatment) at Kurume University Hospital, Japan, between 2004 and 2017. CRS association with MDR1 and CA125 KELIM was examined using Cox proportional hazard regression analyses. Survival curves used Kaplan-Meier method, and survival differences between groups used log-rank test. Overall, 55 patients were classified into CRS1 (n=22), CRS2 (n=19), and CRS3 (n=14). The CRS3 group had a significantly better prognosis than the CRS1 or CRS2 group. CRS, age, and IDS status were clinical prognostic factors for ovarian cancer. MDR1 positivity for excision repair cross-complementing group 1, β-tubulin, and Y-box binding protein-1 occurred in 15, 17, and 11 patients, respectively, but these were not associated with CRS. CA125 KELIM was <0.5 (n=8), 0.5-1.0 (n=30), and ≥ 1.0 (n=17) but not associated with CRS. CRS is reconfirmed as a treatment response predictor for NAC-IDS, but its association with drug resistance factors remains unconfirmed.

Rectal Metastasis from Early-Stage Endometrial Carcinoma Not Associated with Endometriosis: A Case Report and Literature Review

Endometrial cancer (EC) is the third most common malignancy in woman with excellent prognosis when diagnosed in early-stage. Recurrences are extremely rare in Stage I EC especially in rectum when not associated with endometriosis. We present a case of rectal metastasis from endometrial carcinoma after 8 years of primary diagnosis. A review of the literature showed only 6 published cases. Herein we present a 59-year-old woman with a rectal tumor mass. The patient before 8 years was surgically treated for EC Stage IA with bilateral salpingo-oophorectomy and hysterectomy. After ultra-low anterior resection rectum was removed with the tumor. Histology revealed adenocarcinoma with positive immunohistochemistry for CK7, ER, PAX8, Vimentin which confirmed endometrial origin. Endometriosis was not found. Although rectum is a rare site of recurrence from endometrial cancer, rectal tumors should be sampled carefully. Previous patient history and positive immunohistochemistry for EC are in favor of recurrent disease. Screening of colorectal carcinoma should be performed in patients with previous gynecologic diagnosis. Further genetic analysis in bigger case series is needed in order to explain the time and the site of recurrence of early-stage endometrial carcinoma.

Upregulated Nuclear Y-box Binding Protein-1 Expression is Closely Associated with Mammalian Target of Rapamycin Expression in Endometrial Cancer

Enhanced oncogenic Y-box binding protein-1 (YB-1) expression, associated with the aberrant expression of genes involved in cell proliferation, survival, and drug resistance, can predict prognostic outcomes in patients with various malignancies. We examined whether YB-1 could predict prognostic outcomes in patients with endometrial cancer and whether enhanced YB-1 expression affects the expression of mammalian target of rapamycin (mTOR) in endometrial cancer. We examined the expression levels of YB-1 and mTOR in tumor samples of 166 patients with endometrial cancer, including those with endometrioid grade 1-3, serous carcinoma, and stage I-IV disease, who underwent surgery. The expression levels of both molecules were assessed using immunohistochemical analysis. The correlation between the expression levels of YB-1 or mTOR and prognosis was also confirmed.The positivity rate of nuclear YB-1 expression was 9.4%. YB-1 expression was associated with poor progression-free survival (P = 0.012) and overall survival (P = 0.003). Fifty-nine patients (35.5%) exhibited mTOR expression. Nuclear YB-1 expression was also correlated with mTOR expression (P = 0.006). We observed similar results when examining only patients who underwent adjuvant chemotherapy. Enhanced nuclear YB-1 expression could predict poor outcomes in endometrial cancer and was significantly associated with enhanced mTOR expression.