ATRX protein is a potential prognostic marker in clear cell renal cell carcinoma.

Objective: Cancer cells activate either telomerase or alternative lengthening of telomeres (ALT) to maintain telomere length and achieve immortalization. Alpha thalassemia/mental retardation X-linked (ATRX) is involved in chromatin remodeling. Mutations in ATRX genes are associated with the loss of nuclear expression and correlated with the ALT phenotype. ATRX expression has been evaluated in various cancers, especially sarcoma and neuroendocrine tumors, and its clinical significance has been shown to be diverse, depending on the tumor types. The role and prognostic value of ATRX expression in clear cell renal cell carcinoma (CCRCC) have not been elucidated. Methods: We investigated the messenger RNA (mRNA) expression levels of ATRX using the gene expression profiling interactive analysis (GEPIA) database and evaluated the expression of ATRX using immunohistochemical (IHC) staining in 302 CCRCC cases. Results: Loss of ATRX expression was significantly associated with larger tumor size, higher nuclear grade (NG), lymphovascular invasion (LVI), pathologic T (pT) stage, recurrence/metastasis, and stage. Although ATRX was not an independent prognostic factor, patients with loss of ATRX expression showed poor survival. Conclusion: Our findings suggest that loss of ATRX expression could be a potential biomarker for predicting aggressive tumor behavior and poor clinical outcomes in CCRCC.

High MCM6 Expression as a Potential Prognostic Marker in Clear-cell Renal Cell Carcinoma.

AIM: Minichromosome maintenance (MCM) proteins are involved in initiation of DNA replication and cell-cycle progression. Loss of MCM function results in genomic instability and causes carcinogenesis. Among MCM genes, the role and prognostic value of MCM6 expression in clear-cell renal cell carcinoma (ccRCC) has not been elucidated. MATERIALS AND METHODS: We assessed the mRNA expression level of MCM6 using the Gene Expression Profiling Interactive Analysis database and investigated MCM6 protein expression by immunohistochemistry in 238 ccRCC cases. RESULTS: High MCM6 expression was significantly associated with increasing tumor size, pT, stage, tumor necrosis, and metastasis. Furthermore, high MCM6 expression was significantly associated with shorter overall and disease-free survival, and was an independent unfavorable prognostic marker. Regarding patients with metastasis, high MCM6-expressing ccRCC conferred significantly shorter survival than for those with low expression. CONCLUSION: A high MCM6 expression level may be a promising biomarker to predict tumor progression, metastasis, and survival in patients with ccRCC.

Aberrant Expression of E-cadherin, N-cadherin, and P-cadherin in Clear Cell Renal Cell Carcinoma: Association With Adverse Clinicopathologic Factors and Poor Prognosis.

OBJECTIVE: Aberrant expression of cadherins is known to be associated with tumor aggression. However, their role in clear cell renal cell carcinoma (CCRCC) is not well elucidated. This study investigated the expression of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), and placental cadherin (P-cadherin) in CCRCC, and assessed their prognostic significance and clinicopathologic association. MATERIALS AND METHODS: We enrolled 254 patients with CCRCC who underwent radical or partial nephrectomy. E-cadherin, N-cadherin, and P-cadherin expression was evaluated by immunohistochemistry in a tissue microarray. RESULTS: Low E-cadherin expression was associated with larger tumor size, lymphovascular invasion, higher pT stage, lymph node and distant metastasis, and higher stage. High N-cadherin expression was significantly associated with larger tumor size, higher nuclear grade, and tumor necrosis. P-cadherin expression was found to be significantly associated with higher nuclear grade, distant metastasis, and higher stage. Univariate analysis revealed that aberrant expression of the 3 cadherins was significantly related to shorter overall survival (OS). Loss of E-cadherin, high P-cadherin expression, and higher stage were independent prognostic factors for OS. For recurrence-free survival, lymphovascular invasion, high P-cadherin expression, and higher stage were independent prognostic factors. Cadherin switch was significantly associated with aggressive clinicopathologic factors and poor outcomes. CONCLUSIONS: Aberrant expression of E-cadherin, N-cadherin, and P-cadherin was associated with adverse clinicopathologic factors and worse OS. Low E-cadherin and high P-cadherin expression were significantly associated with distant metastasis and independent prognostic factors. Therefore, cadherin expression may be used as a prognostic marker and therapeutic target, and cadherin switch plays an important role in CCRCC progression.

Ovarian Gynandroblastoma with a Juvenile Granulosa Cell Tumor Component in a Postmenopausal Woman: A Case Report and Literature Review.

Gynandroblastoma is an extremely rare sex cord-stromal tumor with both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor) elements. Juvenile granulosa cell tumors are also very rare and are so named because they usually occur in children and adolescents. A 71-year-old woman with right upper quadrant abdominal pain visited our hospital. Pelvic computed tomography showed a large multilocular cystic mass, suspected to be of ovarian origin. We performed a total abdominal hysterectomy (total abdominal hysterectomy was performed) with bilateral salpingooophorectomy. A 13-cm multilocular cystic mass with serous fluid was observed in her right ovary. Upon microscopic examination, the solid component of the mass showed both Sertoli-Leydig cell and juvenile granulosa cell differentiation, which we diagnosed as gynandroblastoma. Gynandroblastoma with a juvenile granulosa cell tumor component is extremely rare and, until now, only six cases have been reported in the English literature. We report the first gynandroblastoma with a juvenile granulosa cell tumor component diagnosed in an elderly patient, along with a literature review.