Endometrioid Carcinoma Grade Research Articles

A case of grade1 follicular lymphoma diagnosed by laparoscopic lymph node resection: differentiating from late lymph node recurrence of endometrial cancer.

Follicular lymphoma is a common hematologic malignancy; however, it is less common among all malignant diseases and is difficult to suspect in advance due to the lack of specific clinical findings. Here, we report a case in which a late recurrence of corpus cancer was first suspected and finally diagnosed as follicular lymphoma. A 67-year-old female presented to our department with enlarged pelvic lymph nodes. She was diagnosed with breast cancer (HER2-posiotive with lymph node metastasis) and corpus cancer (endometrioid carcinoma grade 2, stage IA) 16years prior, received definitive therapy and was followed up. A positron emission tomography scan was performed, and an accumulation of 18F-fluorodeoxyglucose (FDG) was detected in multiple lymph nodes, including the lymph nodes with no change in size or enlargement. We performed laparoscopic resection of the enlarged and FDG-accumulated lymph nodes and a pathological examination. The patient was diagnosed with follicular lymphoma (FL) grade 1 and is currently under observation at the Department of Hematology. FL can be considered when there is a discrepancy between the change in lymph node size and the degree of FDG accumulation. A pathological examination is useful for accurate diagnosis. Therefore, it is important to consider tissue collection; however, care must be taken to minimize the invasiveness of the procedure for the patient.

Coexistence of ovarian cancer and peritoneal tuberculosis: a case report.

Peritoneal tuberculosis (TB) is known to mimic advanced ovarian cancer. In this case report, we describe a unique case of ovarian cancer (endometrioid carcinoma grade 3) at the International Federation of Gynecology and Obstetrics (FIGO) stage IC1 with pulmonary and peritoneal TB, which was suspected preoperatively to be a coexistence of advanced ovarian cancer and pulmonary TB. A 68-year-old woman presented with a prominent abdominal mass and fever. Laboratory investigations, imaging, and sputum analysis indicated a probable diagnosis of ovarian cancer at FIGO stage IIIC, characterized by peritoneal dissemination and para-aortic lymph node metastasis, which was further complicated by coexisting pulmonary TB. Surgical management included total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy. Intraoperatively, the tumor was localized to the right ovary with significant peritoneal thickening and adhesions indicative of peritoneal TB. The surgery was completed without apparent complications. Postoperative histopathological evaluation confirmed grade 3 endometrioid carcinoma in the right ovary along with evidence of peritoneal TB. Given the extent of adhesions attributed to TB, lymph node dissection for staging was deemed challenging and was thus not pursued. Initiation of anti-TB treatment on postoperative day 2 resulted in marked regression of the preoperatively identified pulmonary nodules and para-aortic lymph node enlargement, suggesting their inflammatory origin from TB. Although postoperative chemotherapy is typically advocated for patients with stage IC1 endometrioid carcinoma grade 3, the patient opted against it. Consequently, no adjuvant therapy was administered and the patient remained under close observation.

A phase II trial evaluating the efficacy and safety of repeated high dose medroxyprogesterone acetate (MPA) therapy for patients with recurrent early-stage endometrial cancer or atypical endometrial hyperplasia: Japanese Gynecologic Oncology Group study (JGOG2051/KGOG2031, REMPA trial).

Fertility preserving therapy using medroxyprogesterone acetate (MPA) is an important option for young patients with endometrial cancer or atypical endometrial hyperplasia (AEH). However, the effectiveness and feasibility of repeated MPA therapy for patients with intrauterine recurrence following initial MPA therapy is controversial. Only a few single-institution retrospective studies have been conducted on repeated MPA therapy, therefore, multicenter prospective studies for repeated MPA therapy are highly needed. The aim of this study is to assess whether repeated MPA therapy is effective and feasible for patients with intrauterine recurrence following initial MPA therapy. This is a prospective, single-arm, a multicenter phase II trial on repeated MPA therapy for intrauterine recurrence following fertility-preserving therapy for AEH or stage IA (the International Federation of Gynecology and Obstetrics [FIGO] 2008) non-myoinvasive endometrioid carcinoma grade 1. Patients are treated with oral MPA (500-600 mg/day). Pathologically assessment via dilation and curettage will be performed every 2 months until complete response. The major inclusion criteria are 1) intrauterine recurrence of AEH or stage IA (FIGO 2008) endometrioid carcinoma grade 1 without myometrial invasion or extrauterine spread confirmed by imaging tests after complete remission with the previous MPA therapy. 2) The number of recurrences should be up to twice. 3) histologically diagnosed as AEH or endometrioid carcinoma grade 1, 4) 20-42 years of age, and 5) strong desire and consent for fertility-sparing treatment. The primary endpoint is 2-year recurrence-free survival rate. A total of 115 patients will be enrolled from multiple institutions in Japan and Korea within 4 years and followed up for 2 years. Japan Registry of Clinical Trials Identifier: jRCTs031200256.

In endometrial carcinoma, Ghrelin expression has a diagnostic role, and signal transductors and activators of transcription 5 can be a therapeutic target

Abstract Background and objective Endometrial carcinoma was ranked the sixth most common female cancer worldwide. Previous studies reported that Ghrelin–signal transductors and activators of transcription 5 (STAT5) axis could modulate many tumors’ behavior. Therefore, we investigated the expressions of Ghrelin and STAT5 in endometrioid carcinoma (EC). Moreover, we tried to find a diagnostic marker to differentiate atypical hyperplasia (AH) from well-differentiated EC. Patients and methods One hundred-eight formalin-fixed and paraffin-embedded specimens were cut, and each specimen was stained with STAT5 and Ghrelin separately using immunohistochemistry. Results STAT5 expression was detected in 78.6% of EC. This expression was significantly increased with increasing EC grade (P=0.04) and myometrial invasion depth (P=0.01). In contrast, there was a decrease in Ghrelin expression with lesion progression from cyclic endometrium, and endometrial hyperplasia to EC, which was statistically significant (P=0.002). Moreover, a negative association was noticed between Ghrelin expression and histological grades, depth of myometrial invasion, presence of lymph node metastasis, and tumor stage (P=0.01, 0.05, 0.003, and 0.002, respectively). Conclusion STAT5 is associated with differentiation and invasion in EC and can be targeted for therapeutic management. Additionally, Ghrelin can be a sensitive marker to distinguish AH and well-differentiated EC.

Immunohistochemical Analysis of the Tissue Factor Pathway Inhibitor-2 in Endometrial Clear Cell Carcinoma: A Single-center Retrospective Study.

The tissue factor pathway inhibitor-2 (TFPI2) was recently identified as a diagnostic serum marker for ovarian clear cell carcinoma. Moreover, the immunohistochemical expression of TFPI2 in ovarian clear cell carcinoma was recently reported. This single-center retrospective study aimed to evaluate whether TFPI2 can be a specific biomarker for immunohistological diagnosis of endometrial clear cell carcinoma (ECCC). Immunohistochemical staining of TFPI2 in 55 endometrial carcinomas was evaluated at Nara Medical University Hospital. Thirteen ECCC samples were included as cases and 38 samples were included as a control (endometrioid carcinoma grade 1, 11 cases; grade 2, 11 cases; grade 3, 10 cases; serous carcinoma, 10 cases). The mean ± SD TFPI2 histoscore for diagnosing ECCC was 115.4 ± 87.9, which was significantly higher than that of non-ECCC (21.3 ± 45.9, P = 0.002). The best TFPI2 histoscore value obtained from the analyses of receiver operating characteristic curves for immunohistochemical diagnosis of ECCC was 15. With TFPI2 histoscores ≥15.0 as positive and <15.0 as negative, all 13 ECCC cases (100%) were positive for TFPI2, whereas 11 (26.2%) non-ECCC cases were positive for TFPI2. The sensitivity and specificity of TFPI2 for diagnosing ECCC were 100% and 73.8%, respectively. TFPI2 is expressed in ECCC and is useful for histopathological diagnosis.

Symptomatic women experience long waits for endometrial cancer diagnosis and treatment in Brazil

The aim of this study was to assess the elapsed time for symptomatic women with endometrial carcinoma to achieve diagnosis and treatment and its impact on staging and survival. A cohort study was carried out with 430 women divided into in two groups: “Type I” (n = 289, endometrioid carcinoma grade 1 or 2); “Type II” (n = 141, nonendometrioid, endometrioid carcinoma grade 3, or carcinosarcoma). Clinical information, diagnostic methods, histology, staging, and time elapsed between symptoms-diagnosis-treatment were considered. Descriptive, survival, and regression analyses were performed. The symptom-to-diagnosis interval was 284 and 249 days in Types I and II (p = 0.014), with only 30% getting a diagnosis within 90 days. The diagnosis-to-treatment interval was shorter for Type II (100 vs. 123 days for Type I; p = 0.001). Only 12.5% of Type I and 22.7% of Type II started treatment within 60 days after diagnosis. There was no association between symptom-to-diagnosis interval and staging (p = 0.377). The symptom-to-treatment interval did not change the overall survival for Type I and had a paradoxical effect for Type II, with greater overall survival associated with a longer elapsed time (p = 0.003). Symptomatic Brazilian women with endometrial carcinomas showed very long wait times for diagnosis and treatment, and less than 23% started treatment within the regulatory period of 60 days. This critical situation does not exhibit any clear effect on cancer staging or overall survival, possibly counterbalanced by the faster care of patients with a poor prognosis, such as those with Type II endometrial carcinomas.

Evaluation of the role of intraoperative frozen section and magnetic resonance imaging in endometrial cancer.

To evaluate the accuracy of preoperative endometrial biopsy and magnetic resonance imaging (MRI) of endometrial cancer compared with that of intraoperative frozen section. This retrospective study included 264 patients who underwent surgery with intraoperative frozen section for endometrial cancer at our institution between 2014 and 2018. Diagnosis was determined by histologic type, grade, and myometrial invasion. Concordance rate, sensitivity, and specificity of preoperative diagnosis and intraoperative frozen diagnosis were calculated, in comparison to the final pathologic diagnosis. Preoperative and intraoperative diagnoses showed no statistically significant difference in determining histologic type and grade (P= 0.152). Intraoperative diagnosis showed higher sensitivity for endometrioid carcinoma grade 3 and other types, and higher specificity for grade 1. For myometrial invasion, intraoperative diagnosis showed significantly higher concordance rate than preoperative MRI findings (P< 0.01). Intraoperative diagnosis showed higher sensitivity and specificity in patients with and without myometrial invasion, respectively. Higher agreement between intraoperative and final diagnoses, especially in myometrial invasion, suggests that intraoperative frozen section is a good indicator for appropriate surgical procedure decision making.

Morphometrical Differences among Endometrial Endometrioid Carcinoma Grade 1, Grade 3, and Serous Carcinoma in Endometrial Liquid-Based Cytology Preparations

Introduction: In Japan, the direct smearing preparation (conventional preparation) has been widely used for cytological examination of the endometrium. Problems with the conventional preparation can be dissolved by liquid-based cytology (LBC) preparation. The Yokohama System is a method for reporting endometrial cytology, but the system lumps cancers together and does not distinguish between histological types. The objective of this study was to clarify morphometrical differences among endometrial endometrioid carcinoma grade 1 (G1), grade 3 (G3), and serous carcinoma (Serous) by image analysis of endometrial LBC. Methods: Using Papanicolaou smears prepared by LBC after sampling with a brush from 32 G1, 16 G3, and 16 Serous patients, image analysis was performed concerning the following 11 items: (1) number of layers of cluster, (2) area of cluster, (3) perimeter of cluster, (4) roundness of cluster, (5) complexity of cluster, (6) area of nucleus, (7) perimeter of nucleus, (8) roundness of nucleus, (9) complexity of nucleus, (10) area of nucleolus, and (11) nucleolus/nucleus (N/N) ratio. The data were statistically compared among G1, G3, and Serous. Results: Significant differences were observed in the number of layers of cluster (G1<G3<Serous), area of cluster (G1>G3<Serous), area of nucleus (G1<G3<Serous), area of nucleolus (G1<G3<Serous), roundness of cluster (G1>G3, G1>Serous), complexity of cluster (G1<G3, G1<Serous), roundness of nucleus (G1<Serous), complexity of nucleus (G1>Serous), and N/N ratio (G1>G3, G3<Serous). Conclusion: The number of layers and area of cluster, complexity of cluster, area and complexity of nucleus, area of nucleolus, and N/N ratio were suggested to be useful for the differentiation of histological types among G1, G3, and Serous. Particularly, differences in the number of layers of cluster, size of nucleus, and size of nucleolus among histological types were large and are considered to be potentially effective points of differential diagnosis.

Abnormal accumulation of OFD1 in endometrial cancer with poor prognosis inhibits ciliogenesis.

The aim of the present study was to examine primary cilia in endometrial tissue during the menstrual cycle and to clarify their morphological changes with different grades of endometrial cancer. Images of fluorescence immunostaining taken by confocal microscopy were used to count the number of primary cilia in normal endometrium and endometrioid carcinoma Grade 1 and Grade 3 specimens. To examine the association between autophagy and ciliogenesis in endometrioid carcinoma, the expression of p62/Sequestosome-1, a selective substrate for autophagy, and oral-facial-digital syndrome 1 protein (OFD1), a protein associated with ciliogenesis, were examined using images of fluorescence immunostaining taken by confocal microscopy. The level of p62 expression was confirmed by western blotting. In proliferative and secretory endometrial stromal cells, the percentage of cells that were ciliated was 7.2 and 32.7% (95% confidence interval=21.61-39.79; P<0.01), and the length of the primary cilia was 1.24 µm and 2.34 µm (0.92-1.26; P<0.01), respectively. In stromal cells of endometrioid carcinoma Grade 1 and Grade 3, the percentage of ciliated cells was 13.5 and 2.9% (7.89-15.05; P<0.001), and the length of the primary cilia was 2.02 and 1.14 µm (0.76-0.99; P<0.001), respectively. In both normal menstrual cycle tissue and endometrial carcinomas, the percentage of primary cilia was lower and their length was shorter in tissues with higher proliferative potential. The expression of OFD1 was significantly higher in Grade 3 compared with Grade 1 as indicated by quantifying the intensity of the fluorescence images (133–12248; P=0.046). To the best of our knowledge, this is the first study concerning the distribution of primary cilia in normal endometrium and endometrial cancer tissues. Overall, fewer ciliated cells in the highly malignant endometrial cancer tissues may be associated not only to the proliferation of cancer cells, but also to the excessive accumulation of OFD1 due to dysfunctional autophagy.

Endometrial Cancer After Pancreas-After-Kidney Transplantation: A Case Report and Review of the Literature

As the number of long-term survivors after organ transplantation increases, malignancy has become a problem as a late complication. We herein report a case of endometrial cancer during the follow-up of pancreas transplantation after kidney transplantation. A 49-year-old woman was diagnosed with endometrial cancer. The patient had developed type 1 diabetes at 8 years old and started insulin treatment, and at 29 years old, she started hemodialysis for diabetic nephropathy. At 31 years old, she received living donor kidney transplantation and withdrew from dialysis. Hypoglycemia unawareness began to occur frequently from around 36 years old, and at 48 years old, the patient underwent deceased donor pancreas transplantation after kidney transplantation and achieved insulin independence. At 49 years old, she was diagnosed with endometrial cancer. Surgical treatment (total abdominal hysterectomy with left salpingo-oophorectomy) was performed. The pathologic diagnosis was confirmed as stage 1A uterine endometrioid carcinoma grade 1. The postoperative course was uneventful. She was discharged from our hospital on postoperative day 8. There has been no evidence of recurrence and/or metastasis of endometrial cancer for 16 months since the surgery. Carcinogenesis after pancreas transplantation may be a lethal late complication. It is important to carry out regular screening examinations with carcinogenesis in mind.

Morphological Differences between Liquid-Based Cytology and Conventional Preparation in Endometrial Endometrioid Carcinoma Grade 1 and Grade 3, and the Differentiation of Grades in Each Method

Introduction: Direct smearing preparation (conventional preparation [CP]) has been widely used for endometrial cytology in Japan. In CP, sampling and screening errors are problematic. In liquid-based cytology preparation (LBC), the problems of CP can be solved. But there is a problem that cytological findings of LBC are different from those of CP. The purpose of this study was to evaluate the differences of morphological findings of endometrial cytology between LBC and CP, and the usefulness of the endometrial LBC to differentiate endometrioid carcinoma grade 1 (G1) from grade 3 (G3). Methods: Thirteen cases of endometrioid carcinoma G1, and 5 cases of G3 collected by the Softcyte device and prepared by LBC and CP (split specimen) were used. We focused on the following items: (1) the number of clusters per cm², (2) the number of layers of clusters, (3) area of clusters, (4) perimeter of clusters, (5) roundness of clusters, (6) complexity of clusters, (7) area of nucleus, (8) perimeter of nucleus, (9) roundness of nucleus, (10) complexity of nucleus, (11) area of nucleolus, and (12) nucleolus-nucleus ratio (N/N). Results: Compared with CP, the number of clusters and layers of the clusters in LBC were significantly larger in G1. The area and perimeters of the clusters and the nucleus were significant smaller, and the N/N ratio was greater in LBC than that in CP in both G1 and G3. Regarding morphological differences between G1 and G3 in LBC and CP, the number of layers was significantly larger in G1 than in G3 in LBC and CP. The area of the clusters in LBC was significantly larger in G1 than in G3. The area and perimeters of the nucleus in CP and the area of the nucleolus and N/N ratio in LBC and CP were significantly smaller in G1 than in G3. Conclusion: In the endometrial cytology, it became clear that the cell image was different between LBC and CP and between G1 and G3. By microscopic examination understanding the characteristics of the cell image in LBC, endometrial LBC could be useful to diagnose endometrial carcinoma.

P22.04 Lung Metastasis of Thyroid Transcription Factor 1 Positive Endometrioid Carcinoma; A Case Report

Thyroid transcription factor 1 (TTF-1) is a protein which regulates transcription of genes specific for thyroid, lung, and diencephalon, and is used in anatomic pathology as a marker to determine if a tumor arises from lung or thyroid. TTF-1 positive rate in endometrial carcinoma (Grade 1-2) is as rare as 2%. We present a solitary pulmonary metastasis case from TTF-1 positive endometrioid carcinoma. A 84-year-old woman was addressed to our institution for an abnormal shadow in the chest. Chest CT showed 14mm nodule in the right lower lobe. She had a previous history of surgically resected endometrioid carcinoma (Grade 2) of the uterine corpus. Video assisted thoracic surgery was performed for diagnostic and therapeutic purposes. Intra-operative diagnosis was suspected lung metastasis of endometrioid carcinoma. Immunohistochemical staining revealed positive estrogen receptor, TTF-1 and PAX8. Based on the results, we made a diagnosis of metastatic endometrioid carcinoma. The postoperative course was uneventful. TTF-1 positive endometrioid carcinoma is rare. Medical history and immunohistochemistry are useful for differentiating from primary lung cancer. TTF-1 positive endometrioid carcinomas have reported a poor prognosis and require careful follow-up.

Nuclear morphometry as an adjunct to cytopathologic examination of endometrial brushings on LBC samples: A prospective approach to combined evaluation in endometrial neoplasms and look alikes.

In this study, we aimed to retrospectively investigate and confirm whether atypical nuclear findings in endometrial cytology are useful when assessed by image morphometry in liquid-based cytology (LBC) and compared with microscopic evaluation. In total, 53 cases were selected for this study, including 11 presenting proliferative endometrium, 12 with surface papillary syncytial change with endometrial glandular and stromal breakdown (EGBD-SPSC), 10 endometrioid carcinoma grade 1 (G1-EEC), 10 EEC grade 3 (G3-EEC), and 10 endometrial serous carcinomas (ESC). Nuclear image morphometry for nuclear geometric features (area, grey value, aspect ratio, internuclear distance, nucleolar diameter) was performed using ImageJ computer software. For assessing nucleoli, 3861 nuclei were measured, and for nuclear findings, except for nucleoli, 4036 nuclei were measured in total. (a) Compared with G1-EEC, G3-EEC and ESC presented a marked increase in all six parameters (nuclear enlargement, anisonucleosis, nuclear shade, nuclear shape, irregularity of nuclear arrangement, and nucleolar size). (b) EGBD-SPSC presented a marked increase in two parameters (nuclear shade, nuclear shape) when compared with G1/G3-EEC and ESC. (c) Compared with EGBD-SPSC, EEC and ESC demonstrated a marked increase in nucleolar size (≥2.0μm). (d) ESC presented a marked increase in nucleolar size (≥3.0μm) when compared with G3-EEC. Here we confirmed that atypical nuclear findings evaluated by image morphometry are as useful as microscopic evaluations in endometrial cytology. We believe that the objective evaluation of nucleolar size could contribute to an accurate diagnosis of endometrial-LBC samples.

Correction to: Gaussian mixture model-based cluster analysis of apparent diffusion coefficient values: a novel approach to evaluate uterine endometrioid carcinoma grade

The original version of this article, published on 28 July 2020, unfortunately contained a mistake.

Gaussian mixture model-based cluster analysis of apparent diffusion coefficient values: a novel approach to evaluate uterine endometrioid carcinoma grade.

The purpose of our study was to perform Gaussian mixture model (GMM)-based cluster analysis of the apparent diffusion coefficient (ADC) data of patients with endometrioid carcinoma, and to evaluate the relationship between histological grade and the ratios of the different clusters in each patient. This retrospective study enrolled 122 patients (training: n = 63; and validation: n = 59) imaged between May 2015 and February 2020. In the training cohort, manual segmentation was performed on the ADC maps to obtain the ADC data of each patient, and these ADC data were summated to obtain the "All-patient" ADC data. Cluster analysis (three clusters) was performed on this All-patient ADC data, and the ADC ranges of each cluster were defined as follows: cluster 1, 490-699 × 10-6mm2/s; cluster 2, 700-932 × 10-6mm2/s; and cluster 3, over 933 × 10-6mm2/s. In the training and validation cohorts, the ADC data of each patient was classified into three clusters according to these ADC ranges. The cluster ratios of each patient were calculated and compared with histological grade. In the training cohort, a significant positive correlation was found between the cluster 1 ratio and histological grade (ρ = 0.34, p = 0.0059). The cluster 1 ratios of high-grade lesions (grade 3) were significantly higher than those of low-grade lesions (grades 1 and 2) (p = 0.0084). A similar significant positive correlation was found between the cluster 1 ratio and histological grade in the validation cohort (ρ = 0.44, p = 0.0006). The cluster 1 ratio containing voxels with low ADC was significantly correlated with the histological grade of endometrioid carcinoma. • We performed Gaussian mixture model (GMM)-based cluster analysis of the apparent diffusion coefficient (ADC) data of patients with endometrioid carcinoma. • The cluster 1 ratio, which included low ADC values, was significantly positive correlated with histological grade in the training and validation cohorts. • The GMM-based cluster analysis of voxel-based ADC data was effective for grading endometrioid carcinoma.

Equivalent Survival of p53 Mutated Endometrial Endometrioid Carcinoma Grade 3 and Endometrial Serous Carcinoma.

TP53 status is the most important prognostic biomarker in endometrial carcinoma. We asked the question whether p53 mutated endometrial endometrioid carcinomas grade 3 (EEC3) or endometrial serous carcinomas (ESC), the latter ubiquitously harboring TP53 mutation, have different outcomes. TP53 mutation status was assessed by surrogate p53 immunohistochemistry on 326 EEC3 and ESC from 2 major cancer centers in Canada. Mutant-type p53 expression, including overexpression, complete absence, or cytoplasmic expression, was distinguished from the wild-type pattern. Statistical associations with clinico-pathological parameter, other key biomarkers, and survival analyses were performed. P53 mutant-type immunohistochemistry was observed in all 126 ESC and in 47/200 (23.5%) EEC3. ESC and p53 mutated EEC3 had an unfavorable outcome compared with p53 wild-type EEC3 (hazard ratio=2.37, 95% confidence interval=1.48-3.80, P=0.003, hazard ratio=2.19, 95% confidence interval=1.16-4.12, P=0.016, respectively) in multivariable analyses adjusted for age, stage, center, and presence of lymph-vascular invasion. There was no significant difference in survival between ESC and p53 mutated EEC3 in multivariable analysis. Furthermore, p53 mutated EEC3 and ESC almost completely overlapped in univariate survival analysis when mismatch repair (MMR)-deficient cases were excluded, which suggests that EEC3 harboring combined MMR deficiency and TP53 mutations behave more according to the MMR status. Significant differences between p53 mutated MMR-proficient EEC3 and ESC in PTEN and p16 expression status remained. p53 mutated, MMR-proficient EEC3 and ESC have overlapping survival significantly different from p53 wild-type EEC3, which justifies a similar treatment with current non-targeted standard therapy. Although this is so, separate classification should continue due to biological differences that will become important for future targeted therapy.

Bmi-1 Immunohistochemical Expression in Endometrial Carcinoma is Correlated with Prognostic Activity.

Background and objectives: B-lymphoma Mo-MLV insertion region 1 (Bmi-1) is a stem cell factor that is overexpressed in various human cancer tissues. It has been implicated in cancer cell proliferation, cell invasion, distant metastasis, and chemosensitivity, and is associated with patient survival. Several reports have also identified Bmi-1 protein overexpression in endometrial carcinoma; however, the relationship between Bmi-1 expression and its significance as a clinicopathological parameter is still insufficiently understood. Accordingly, the present study aimed to clarify whether immunohistochemical staining for Bmi-1 in human endometrial carcinoma and normal endometrial tissues can be used as a prognostic and cell proliferation marker. Materials and Methods: Bmi-1 expression was assessed in endometrioid carcinoma (grade 1–3) and normal endometrial tissues (in the proliferative and secretory phases) by immunohistochemistry; protein expression was evaluated using the nuclear labeling index (%) in the hot spot. Furthermore, we examined other independent prognostic and proliferation markers, including the protein levels of Ki-67, p53, and cyclin A utilizing semi-serial sections of endometrial carcinoma tissues. Results: The expression of the Bmi-1 protein was significantly higher in all grades of endometrial carcinoma than in the secretory phase of normal tissues. Moreover, Bmi-1 levels tended to be higher in G2 and G3 tissues than in G1 tissue, without reaching significance. Bmi-1 expression showed no notable differences among International Federation of Gynecology and Obstetrics (FIGO) stages in endometrial carcinoma. Furthermore, we observed a significant positive relationship between Bmi-1 and Ki-67, cyclin A, or p53 by Spearman’s rank correlation test, implying that high Bmi-1 expression can be an independent prognostic marker in endometrial carcinoma. Conclusions: Our study suggests that Bmi-1 levels in endometrial carcinoma tissues may be useful as a reliable proliferation and prognostic biomarker. Recently, the promise of anti-Bmi-1 strategies for the treatment of endometrial carcinoma has been detected. Our results provide fundamental data regarding this anti-Bmi-1 strategy.

Clinicopathological Correlation of Uterine Corpus Tumors: A Study of 433 Cases

Uterine corpus tumors are one of the most common reasons for morbidity and mortality of women around the world, and histopathological diagnosis is the key for better management of the patients. To study the histopathology of uterine tumors, classify them as per WHO 2014 classification and correlate with clinical parameters. A five-year study was conducted on 433 histopathologically diagnosed cases of uterine corpus tumors. Benign tumors were the most common (95.6%) followed by malignant (3.9%) and borderline (0.5%). Leiomyoma was the most common benign tumor (91.2%). Majority of the cases were multiparous females (88.6%) in fourth and fifth decades of life (77%) and presenting with heavy menstrual bleeding (35.9%). The most location was intramural (68.9%). Cellular leiomyoma (1.8%) was the most common histologic variant; the secondary change was hyalinization (27.8%). Endometrial carcinoma was the most common malignant tumor (3%) followed by leiomyosarcoma (0.5%) and adenosarcoma (0.2%). Majority of the women with endometrial carcinoma were multiparous (76.9%) and belonging to the age-group of 50–59 years (38.4%). The most common symptom was postmenopausal bleeding (76.9%). Endometrioid carcinoma grade I (75%) was the most common type of endometrial carcinoma. Other lesions were adenomyoma (N = 17), STUMP (N = 2), and one case each of adenomatoid tumor, endometrial stromal nodule and secondary tumor. Benign tumors were more common than malignant tumors. Leiomyoma was the most common benign tumor, and endometrial carcinoma was the most common malignant tumor. Many uterine tumors present with similar clinical features. However, histopathology plays an important role in the accurate diagnosis of different types of tumors and thus helps in providing the patient with appropriate management.

Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies).

Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.

Hysteroscopic morphological pattern reflects histological grade of endometrial cancer.

To examine the hysteroscopic morphological features in each histological grade of endometrial cancer, and to distinguish high- and low-grade cancer and low-grade cancer and atypical endometrial hyperplasia (AEH), using hysteroscopy. In total, 135 patients who underwent hysterectomy after hysteroscopy were analyzed. They were divided into four categories: benign lesion; AEH; low-grade cancer, including endometrioid carcinoma grades 1 and 2 (G1/2); and high-grade cancer, including endometrioid carcinoma grade 3 and other high-grade carcinomas (G3/others). Three blinded gynecologic oncologists independently evaluated hysteroscopic video images for abnormal vessels, surface smoothness, papillary structure and polypoid structure. Prevalence rates of each finding were compared between the four categories. The accuracy of blind biopsy in outpatient settings and hysteroscopic endometrial biopsy in the four categories were also investigated. The number of patients with benign lesions, AEH, G1/2 and G3/others was 8, 7, 84 and 36, respectively. Patients with G3/others exhibited more polypoid (86% vs 61%, P = 0.0095) and less papillary (59% vs 80%, P = 0.023) structures than those exhibited by patients with G1/2. AEH and G1/2 were indistinguishable using hysteroscopy. Hysteroscopic biopsy was more accurate than outpatient biopsy in patients with G3/others (84% vs 52%, respectively, P = 0.010). Both biopsies were not sufficiently accurate to diagnose AEH (outpatient; 0%, hysteroscopic; 57%). Hysteroscopic papillary and polypoid structures can help distinguish between high- and low-grade cancer. Hysteroscopic differentiation between AEH and low-grade cancer is difficult. These findings are considerable in preoperative assessment to determine adequate surgical strategies.