Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival and Recurrence.

This study aimed to evaluate the efficacy of the 2020 European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for endometrial cancer (EC). Additionally, a novel risk category incorporating clinicopathological and molecular factors was introduced. The predictive value of this new category for recurrence and survival in Korean patients with EC was assessed, and comparisons were made with the 2013 and 2016 European Society of Medical Oncology (ESMO) risk classifications. Patients with EC were categorized into the POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-aberrant (P53abn), and nonspecific molecular profile (NSMP) subtypes. Recurrence, survival, and adjuvant therapy were assessed according to each classification. Notably, patients with the POLEmut subtype showed no relapse, while patients with the P53abn subtype exhibited higher recurrence (31.8%) and mortality rates (31.8%). Regarding adjuvant therapy, 33.3% of low-risk patients were overtreated according to the 2020 ESGO/ESTRO/ESP guidelines. Overall and progression-free survival differed significantly across molecular classifications, with the POLEmut subtype showing the best and the P53abn subtype showing the worst outcomes. The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.

Clinicopathologic significance of mismatch repair protein expression in endometrioid endometrial cancer.

OBJECTIVE: To evaluate the association between mismatch repair (MMR) protein expression and clinico-pathologic outcomes in patients with endometrioid endometrial cancer (EC). MATERIALS AND METHODS: A retrospective review of the clinico-pathologic outcomes was performed on patients who were diagnosed with EC and had results of MMR protein immunohistochemistry. MMR-deficient (MMR-d) was defined as absence of expression in any of the 4 MMR proteins (MLH1, MSH2, MSH6, and PMS2). Demographics, pathologic variables, and survival outcomes were compared according to the MMR status. RESULTS: A total of 193 EC patients with available MMR expression data were included, of whom 163 patients had endometrioid type EC. Overall, 44 patients (27.0%) were classified as MMR-d. Compared with MMR-proficient (MMR-p) group, MMR-d group was associated with more frequent lymphovascular space invasion (LVSI, p = 0.001). MMR-d was also related with higher risk of lymph node (LN) metastasis in endometrioid type EC (p = 0.008), especially para-aortic LN metastasis. During the median follow-up period of 19.1 months (1-44.5), MMR-d group, especially MLH1/PMS2 subgroup, showed a tendency of reduced PFS (p = 0.036 and p = 0.008, respectively). On Cox regression analysis, however, LN metastasis remained as the only independent risk factor for PFS (p = 0.004) in endometrioid EC, and MLH1/PMS2 loss showed a marginally significant association (p = 0.054). CONCLUSION: Our findings of the associations between MMR deficiency and poor prognostic factors, such as LVSI and LN metastasis, may suggest the prognostic value of MMR status in EC and need further prospective validation studies.

Radiologic Findings of Mesonephric-Like Adenocarcinoma of the Uterine Corpus: A Case Report.

According to the 2020 World Health Organization classification, mesonephric-like adenocarcinoma (MLA) is newly categorized as a subtype of endometrial carcinoma and remains a relatively unknown disease owing to its rarity. To the best of our knowledge, radiological findings of MLA have not been reported in the English literature. The uterine MLAs show a worse clinical prognosis and a more aggressive biological behavior than the usual endometrial carcinoma. Herein, we present the imaging findings of a 65-year-old female with a MLA in the uterine corpus. The tumor was a solid endometrial mass with deep myometrial invasion, poor contrast enhancement, and moderate diffusion restriction.

Clear Cell Borderline Tumor of the Ovary: A Case Report.

Clear cell borderline ovarian tumor (CCBOT) is quite rare, and only a few cases of CCBOT have been reported. Unlike most borderline ovarian tumors, CCBOTs appear solid because they are almost always pathologically adenofibromatous. Herein, we report the MRI findings of a CCBOT discovered in a 22-year-old female.

Lymphocyte activation gene (LAG)-3 is a potential immunotherapeutic target for microsatellite stable, programmed death-ligand 1 (PD-L1)-positive endometrioid endometrial cancer.

OBJECTIVE: Immune checkpoint inhibitors have been widely used in the treatment of endometrial cancer (EC) with microsatellite instability-hypermutated (MSI-H). However, there is an unmet need for microsatellite stable (MSS) EC because of their modest activity. This study aimed to identify potential immune-related biomarkers in MSS EC. METHODS: One hundred and twenty-three patients with EC who underwent hysterectomy were enrolled. MSI status was determined using MSI analysis and/or immunohistochemical staining for mismatch repair proteins. Immunohistochemical analysis of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), cluster of differentiation 3 (CD3), CD8, lymphocyte activation gene-3 (LAG-3), indoleamine 2,3-dioxygenase 1 (IDO1), phosphatase and tensin homolog (PTEN), p53, AT-rich interactive domain-containing protein 1A (ARID1A), and ß-catenin was performed using tissue microarray blocks. RESULTS: Among 123 patients, 95 (77.2%) were classified as having MSS. Within EC with MSS, PD-L1 positivity was significantly associated with positive PD-1 (p<0.001), CTLA-4 (p<0.001), CD3 (p=0.002), CD8 (p<0.001), and LAG-3 (p<0.001). In the univariate analysis, positive PD-1 (odds ratio [OR]=9.281; 95% confidence interval [CI]=2.560-33.653; p<0.001), CTLA-4 (OR=5.33; 95% CI=1.418-19.307; p=0.005), CD3 (OR=5.571; 95% CI=1.746-17.775; p=0.004), CD8 (OR=6.909; 95% CI=2.647-18.037; p<0.001), and LAG-3 (OR=9.75; 95% CI=1.947-48.828; p=0.005) were significantly associated with PD-L1 positivity in MSS EC. In the multivariate analysis, LAG-3 demonstrated a significant association with positive PD-L1 expression in MSS EC (OR=5.061; 95% CI=1.534-16.693; p=0.023). CONCLUSION: In patients with MSS EC harboring PD-L1, LAG-3 may be a potential immunotherapeutic target. Clinical trials investigating the role of anti-LAG-3 antibodies, alone or in combination with other immunotherapies, are warranted.

Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset.

OBJECTIVE: Recent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS). METHODS: Archival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were analyzed and compared according to the stage and histological type. Additionally, survival effects of specific mutated genes were analyzed. RESULTS: Somatic mutation patterns of 38 genes were identified in 263 EC samples, and the most commonly mutated genes were PTEN and PIK3CA. PTEN was the most common in endometrioid histology, while PPP2R1A was the most commonly mutated gene in serous histology. The mutation rates of PPP2R1A and TP53 were significantly higher in advanced EC sample than in stage I samples (22.5% vs. 4.3% [p<0.001] and 8.4% vs. 1.4% [p=0.021], respectively). Survival analysis of the total population and endometrioid subgroup revealed that patients with PPP2R1A mutations had significantly shorter survival than did those without mutations (p=0.005 and p<0.001, respectively). CONCLUSION: PPP2R1A mutations might have a role in dismal prognosis of advanced EC.

A rare case of gastric-type mucinous adenocarcinoma in a woman with Peutz-Jeghers syndrome.

Adenocarcinoma of the cervix is less common than squamous cell carcinoma. Minimal deviation adenocarcinoma (adenoma malignum) is considered an extremely well-differentiated variant of GAS. An association exists between GAS and Peutz-Jeghers syndrome, which is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps in the gastrointestinal tracts. The incidence of GAS in patients with Peutz-Jeghers syndrome is estimated to be 11-17%. We present a rare case of adenoma malignum, diagnosed using colposcopic biopsy in a woman with Peutz-Jeghers syndrome, which was histopathologically confirmed to be GAS after surgery.

Dual immunostaining of cervical cytology specimens with atypical squamous cells for p16/Ki-67 does not exclude the existence of a high-grade squamous intraepithelial lesion.

This study was conducted to evaluate the accuracy of p16/Ki-67 dual immunostaining compared to high-risk human papillomavirus (HR-HPV) DNA testing for cervical intraepithelial neoplasia (CIN) in women with atypical squamous cells, cytology not excluding high-grade squamous intraepithelial lesion (ASC-H). Data were collected from 73 patients diagnosed to have ASC-H on a Pap smear who were HPV genotyped and had histological examination of a cervical biopsy. The CINtecPLUS kit was used on residual liquid-based material, and the immunoreactivity of dual-stained cells was graded according to the number as follows: G1 (1-5 positive cells), G2 (6-10), G3 (11-20), and G4 (> 20). Accuracy was evaluated based on the histological examination of colposcopy-guided biopsy or cervical conization on follow-up. Of the 70 patients with available data, positive p16/Ki-67 was associated with histological severity as follows: 15% in negative histology, 67% in CIN 1, 90% in CIN 2, and 100% in CIN 3. The average grade of positive p16/Ki-67 staining also increased from 0.2 in histologically negative cases to 1.2 in CIN 1, 2.4 in CIN 2, and 2.9 in CIN 3 (p < 0.01). For patients with CIN 2 or higher, p16/Ki-67 had a sensitivity of 94.6% and a specificity of 75.8%, while HR-HPV testing showed a sensitivity of 67.6% and a specificity of 66.7%. p16/Ki-67 immunostaining demonstrated better accuracy than HR-HPV for detecting CIN 2 or higher in patients with ASC-H cytology. Given the higher concordance with histological diagnosis, the grading system of positive p16/Ki-67 can be a useful adjunct for predicting high-grade lesions in clinical practice.

Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia.

OBJECTIVE: To evaluate the prevalence of concurrent endometrial carcinoma in women diagnosed with atypical endometrial hyperplasia (AEH) by endometrial biopsy. STUDY DESIGN: We retrospectively analyzed the medical records of 126 patients who underwent hysterectomies for AEH diagnosed by endometrial biopsy from 1999 to 2008. AEH was initially diagnosed by dilatation and curettage (98 cases) or endometrial biopsy with a Z-sampler (24 cases). The remaining four cases were diagnosed by hysteroscopic polypectomy. The results of the endometrial biopsies were graded on an ordinal scale and were compared with pathologic features obtained at the hysterectomy. RESULTS: In patients preoperatively diagnosed with AEH by biopsy, hysterectomy specimens revealed a rate of simple or complex endometrial hyperplasia without atypia of 27% with AEH and normal proliferative phases found in 54.7 and 7.9% of specimens, respectively. The incidence of endometrial carcinoma was considerably high (13/126, 10.3%). Eleven of 13 cases were confined to the endometrium and the remaining two were located at the adenomyosis without myometrial invasion. All patients with endometrial carcinoma displayed coexisting atypical complex hyperplasia following hysterectomy. CONCLUSIONS: Biopsy specimens showing AEH, particularly atypical complex hyperplasia, are associated with a risk of coexisting endometrial carcinoma. When considering management strategies for women with a biopsy diagnosis of AEH, clinicians should take into account the considerable rate of concurrent endometrial cancer and the discrepancy with pathologic diagnosis. Treatment modalities may differ depending on population as the rates of concurrent endometrial cancer with AEH and myometrial invasion vary by geographical location.

Heterogeneity of invasive ductal carcinoma: proposal for a hypothetical classification.

To investigate what heterogeneity exists in breast cancer, 228 consecutive patients with operable invasive duetal carcinoma (IDC), not otherwise specified, were categorized on the basis of the horizontal progression model of carcinogenesis. Using the reversed Black's nuclear grade (RBNG) in the IDC component and the association of ductal carcinoma in situ (DCIS), the patients were classified into pure IDC (IDC de novo or ab initio) as Group I, non-high grade (RBNG 1 and 2) IDC with DCIS as Group II, and high grade (RBNG 3) IDC with DCIS as Group III. The Groups classified in the present study appeared as a prognostic factor independent of known prognostic and predictive factors in multivariate test. Group I had the worst prognosis among the three groups and was the most non-responsive to tamoxifen. After performing stratifying analyses by group, it was found that metastasis-free survival was statistically associated with the status of hormone receptors estrogen receptor and progesterone receptor and tamoxifen therapy only in Group II. In addition, the status of c-erbB-2 expression had prognostic significance only within the Group III. Our results may be used to frame an alternative hypothetical model for breast cancer evolution and will lead us to reconsider the tailoring of the comprehensive therapeutic modality used at the present time.

Complications arising in twin pregnancy: findings of prenatal ultrasonography.

Multifetal gestations are high-risk pregnancies involving higher perinatal morbidity and mortality, and are subject to unique complications including twin oligohydramnios-polyhydramnios sequence, twin-to-twin transfusion syndrome, acardiac twins, conjoined twins, co-twin demise, and heterotopic pregnancies. The purpose of this study is to describe the prenatal ultrasonographic and pathologic findings of these complications.