Microcystic, elongated, and fragmented (MELF) pattern is seen in the invasive front of some endometrial endometrioid carcinomas. Although MELF pattern can be expected as an indicator of patient outcomes, its prognostic significance remains unclear. This study was conducted to elucidate clinicopathologic features and the prognostic impact of MELF pattern in patients with endometrial endometrioid carcinoma. We retrospectively analyzed data of 479 consecutive patients with endometrial endometrioid carcinoma that had been surgically resected. In 45 of 427 patients (11%) with low-grade endometrioid carcinoma, MELF pattern was found, but it was found in none of the 52 patients with high-grade endometrioid carcinoma. Among the patients with low-grade endometrioid carcinoma, MELF pattern was associated significantly with larger tumor size, myometrial invasion of more than 50%, advanced International Federation of Gynecology and Obstetrics stages, lymphovascular space invasion, lymph node metastasis, papillary architecture, and mucinous differentiation. However, survival analysis revealed that the patients with MELF pattern showed no significantly worse prognosis than those without MELF pattern either in disease-specific survival or in recurrence-free survival. MELF was not a significant prognosticator after adjustment for International Federation of Gynecology and Obstetrics stage (disease-specific survival [hazard ratio, 1.47; 95% confidence interval, 0.28-7.67; P=0.64], recurrence-free survival [hazard ratio, 0.98, 95% confidence interval, 0.32-2.99, P=0.98]). Immunohistochemical analysis revealed that MELF pattern was positive for p16 and p21 and almost negative for Ki-67 labeling, which suggested that tumor cells in MELF pattern were involved in growth arrest or cellular senescence. We conclude that MELF pattern could have little impact on outcomes of patients with low-grade endometrial endometrioid carcinoma.
Atypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear β-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions.
Decreased cell adhesion has been reported as a significant negative prognostic factor of lung cancer. However, the molecular mechanisms responsible for the cell incohesiveness in lung cancer have not yet been elucidated in detail. We herein describe a rare histological variant of lung adenocarcinoma consisting almost entirely of individual cancer cells spreading in alveolar spaces in an incohesive pattern. A whole exome analysis of this case showed no genomic abnormalities in CDH1 or other genes encoding cell adhesion molecules. However, whole mRNA sequencing revealed that this case had an extremely high expression level of mucin 21 (MUC21), a mucin molecule that was previously shown to inhibit cell‐cell and cell‐matrix adhesion. The strong membranous expression of MUC21 was found on cancer cells using mAbs recognizing different O‐glycosylated forms of MUC21. An immunohistochemical analysis of an unselected series of lung adenocarcinoma confirmed that the strong membranous expression of MUC21 correlated with incohesiveness. Thus, MUC21 could be a promising biomarker with potential diagnostic and therapeutic applications for lung adenocarcinoma showing cell incohesiveness.
A 69-year-old man presented with progressive paralysis of the right arm and leg with a past history of metastatic rectal cancer. Magnetic resonance imaging showed a cystic mass lesion posterior to the odontoid process. Under a preoperative diagnosis of intradural extramedullary tumor, partial transcondylectomy and C1 hemilaminectomy were performed, and the cyst was removed through a transdural approach, decompressing the medulla oblongata and the cervical spinal cord. The histological diagnosis was juxtafacet cyst (ganglion cyst). An atlantoaxial intraspinal juxtafacet cyst at the level of the odontoid process is extremely rare. In our case, the cyst was removed using a posterior approach, resulting in rapid improvement in symptoms.
SLUG expression could be correlated with TP53 mutational status and could be involved in therapeutic resistance resulting in tumour recurrence. A high expression level of SLUG can be an indicator of recurrence and a therapeutic target for long-term remission in high-grade endometrial carcinomas.
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