When epithelial cells in vivo are stimulated to proliferate, they crowd and often grow in height. These processes are likely to implicate dynamic interactions among lateral membranous proteins, such as cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member. Pulmonary epithelial cell lines that express CADM1, named NCI-H441 and RLE-6TN, were grown to become overconfluent in the polarized 2D culture system, and were examined for the expression of CADM1. Western analyses showed that the CADM1 expression levels increased gradually up to 3 times in a cell density-dependent manner. Confocal microscopic observations revealed dense immunostaining for CADM1 on the lateral membrane. In the overconfluent monolayers, CADM1 knockdown was achieved by two methods using CADM1-targeting siRNA and an anti-CADM1 neutralizing antibody. Antibody treatment experiments were also done on 6 other epithelial cell lines expressing CADM1. The CADM1 expression levels were reduced roughly by half, in association with cell height decrease by half in 3 lines. TUNEL assays revealed that the CADM1 knockdown increased the proportion of TUNEL-positive apoptotic cells approximately 10 folds. Increased expression of CADM1 appeared to contribute to cell survival in crowded epithelial monolayers.

Miyagawa C, et al. J Gynecol Oncol. 2023 Feb;34:e47. https://doi.org/10.3802/jgo.2023.34.e47

Background: This study aimed to establish an evaluation method for detecting uterine sarcoma with 100% sensitivity using MRI and serum LDH levels. Methods: One evaluator reviewed the MRI images and LDH values of a total of 1801 cases, including 36 cases of uterine sarcoma and 1765 cases of uterine fibroids. The reproducibility of the algorithm was also examined by four evaluators with different imaging experience and abilities, using a test set of 61 cases, including 14 cases of uterine sarcoma. Results: From the MRI images and LDH values of 1801 cases of uterine sarcoma and uterine fibroids, we found that all sarcomas were included in the group with a high T2WI and either a high T1WI, an unclear margin, or high LDH values. In addition, when cases with DWI were examined, all sarcomas had high DWI. Among the 36 sarcoma cases, the group with positive findings for T2WI, T1WI, margins, and serum LDH levels all had a poor prognosis (p = 0.015). The reproducibility of the algorithm was examined by four evaluators and the sensitivity of sarcoma detection ranged from 71% to 93%. Conclusion: We established an algorithm to distinguish uterine sarcoma if tumors in the myometrium with low T2WI and DWI are present.

The clinicopathological, immunohistochemical, and molecular characteristics of α-fetoprotein (AFP)-producing endometrial carcinoma (AFP+ EC) are poorly understood. From 284 cases of endometrial carcinoma in our pathology archive, we identified five cases (1.8%) of AFP+ EC with fetal gut–like (4/5) and/or hepatoid (2/5) morphology. All cases exhibited lymphovascular infiltration. In addition, 24 cases of endometrial carcinoma with elevated serum AFP levels were retrieved from the literature. The patient age ranged from 44 to 86 years (median: 63). Of 26 cases whose FIGO (International Federation of Gynecology and Obstetrics) stage and follow-up information was available (mean follow-up 24 months), 15 were stage I or II and 11 were stage III or IV. Even in stage I or II disease, death or relapse occurred in more than half of the patients (8/15). Detailed analysis of our five cases revealed that, on immunohistochemistry, AFP+ EC was positive for SALL4 (4/5), AFP (3/5), and HNF1β (4/5) in >50% of neoplastic cells and negative for estrogen and progesterone receptors (5/5), PAX8 (4/5), and napsin A (5/5). Four cases exhibited aberrant p53 immunohistochemistry and were confirmed to harbor TP53 mutations by direct sequencing. No mutation was found in POLE, CTNNB1, or KRAS. In conclusion, AFP+ EC merits recognition as a distinct subtype of endometrial carcinoma, which occurs in 1.8% of endometrial carcinoma cases, are associated with TP53 abnormalities, exhibit lymphovascular infiltration, and can show distant metastasis even when treated in early stage.

Yamanishi Y, et al. J Gynecol Oncol. 2025 Apr;36:e58. https://doi.org/10.3802/jgo.2025.36.e58

Objective: The aim of the study was to characterize magnetic resonance imaging findings in patients with recurrent ovarian adult granulosa cell tumors (AGCTs). Methods: Clinical and magnetic resonance imaging manifestations of recurrent AGCTs were evaluated in 11 patients. Results: Initial recurrences of AGCT were diagnosed between 13 months and 30 years (mean, 11.3 years). Recurrent tumors were located in the pelvic peritoneum, the abdominal peritoneum, the retroperitoneum, and bone. The number of recurrent tumors varied from 1 to 5. Tumors varied in morphology and all margins were well circumscribed. The internal structures noted were as follows: multilocular cystic and solid and cystic. Furthermore, internal hemorrhage and sponge-like multicystic components were identified. Conclusions: Ovarian AGCTs recurred in the pelvic peritoneum, abdominal peritoneum, and the retroperitoneal lymph nodes. Large recurrent AGCTs were commonly well circumscribed, round or lobulated, and multilocular cystic or solid and cystic. Moreover, they frequently included internal hemorrhage and sponge-like multicystic components.