PTEN Expression in Mucinous Prostatic Adenocarcinoma, Prostatic Adenocarcinoma With Mucinous Features, and Adjacent Conventional Prostatic Adenocarcinoma: A Multi-institutional Study of 92 Cases.

Recent studies have demonstrated that most patients with mucinous prostatic adenocarcinoma may have a better prognosis than those with conventional prostatic adenocarcinoma; however, the mechanism remains unclear. Loss of phosphatase and tensin homolog (PTEN) expression is known to occur in aggressive high-grade prostatic adenocarcinoma, but expression in mucinous prostatic adenocarcinoma has not been well characterized. In this study, we sought to analyze PTEN expression in mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma. Cases were obtained from the Urologic Pathology files of 3 major academic institutions. Ninety-two cases were identified. PTEN expression was positive in the mucinous component of 79/92 (86%) cases. Concordant positive expression of PTEN between mucinous prostatic adenocarcinoma, prostatic adenocarcinoma with mucinous features, and the adjacent conventional prostatic adenocarcinoma was present in 60/79 (76%) cases. The fact that 86% of cases of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were positive for PTEN despite relatively high Gleason scores is in keeping with the fact that these tumors may be less aggressive than conventional prostatic adenocarcinoma without associated extraluminal mucinous components. In 76% of cases, the expression profiles (PTEN positive or negative) of mucinous prostatic adenocarcinoma and prostatic adenocarcinoma with mucinous features were similar to those of the adjacent conventional prostatic adenocarcinoma, implying that they may likely be clonal from a molecular standpoint. In addition, it is highly conceivable that the subset of PTEN-negative mucinous tumors may still have a relatively good prognosis due to a different/PTEN-independent protective pathway or mechanism.

The Paris system for reporting urinary cytology improves correlation with surgical pathology biopsy diagnoses of the lower urinary tract.

INTRODUCTION: The current study seeks to compare both the original diagnoses (OD) and the updated Paris system diagnoses (PD) of urinary cytology specimens to the corresponding surgical pathology (biopsy) diagnoses (SD) to determine which diagnostic paradigm (OD vs PD) has a stronger correlation to the SD. DESIGN: 56 cases from 34 patients that had a malignant SD associated with a corresponding cytology specimen from the same location within up to 90 days of the biopsy procedure were selected. We reviewed the cytology specimens and assigned a PD to each case. We then compared each OD and each PD to the corresponding SD. Correspondence was defined as when the SD had the same result or equal weight as either cytopathologic diagnosis. RESULTS: Of the 47 cases with an available SD, the PD alone corresponded in 32%, both PD and OD corresponded in 26%, neither corresponded in 42%. The OD in isolation did not correspond to the SD in any cases, indicating superior correlation with the PD as compared to the OD (P = 0.0002). Of the 15 cases where the PD corresponded, 11/15 were from the lower tract and the remaining 4 were from the upper tract, indicating superior correlation with the PD in specimens from the lower urinary tract (P = 0.034). In the 27 cases where the PD alone and "both" the PD and the OD correlated to the SD, 9/27 were from the upper tract and 18/27 were from the lower tract, indicating further support for increased correlation between the cytopathology and biopsy diagnoses in the lower urinary tract above the upper tract (P = 0.032). CONCLUSION: When applied, the PD has a stronger correlation to the SD, particularly when the biopsies are from the lower urinary tract. Further study with more cases is required to support this significant association.

Federation Nationale des Centers de Lutte Contre le Cancer grading of soft tissue sarcomas on needle core biopsies using surrogate markers.

Needle core biopsy (NCB) of soft tissue sarcomas (STSs) presents problems for French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) histological grading because small sample size hinders determination of necrosis and mitotic activity. We graded 53 STSs on NCB using a modified FNCLCC grading system that substitutes Ki-67 immunoexpression for mitotic count and uses a radiological assessment of necrosis, and compared the results with those obtained by conventional FNCLCC grading of the corresponding untreated, surgically resected specimen. Forty-eight of the 53 tumors were classified as malignant on NCB (concordance = 91%). The modified FNCLCC grade correctly separated high-grade (grades II and III) from low-grade sarcomas in 70% of cases and predicted the traditional FNCLCC grade given to the resected specimen in 49% of cases. Ki-67 scores of 2 or 3 were observed in 5 tumors classified as low-grade neoplasms on NCB but upgraded to a high-grade dedifferentiated liposarcoma on resection. Underestimated NCB grades were commonly encountered with lipomatous tumors due to sampling error, whereas Ki-67 or radiologic necrosis scores higher than the corresponding histological scores were responsible for the vast majority of overestimated NCB grades. Our FNCLCC grading scheme replacing conventional mitosis counting and histologic assessment of necrosis with surrogate markers is useful in separating high- and low-grade STSs on NCB for STS treatment planning. High Ki-67 rate should raise suspicion of a higher-grade component, particularly with fatty tumors.

Absent Aortic Valve in DiGeorge Syndrome.

A 20-week-old fetus with the 22q11.2 deletion characteristic of DiGeorge syndrome is described with vertebral segmentation abnormalities and complex cardiovascular anomalies including an absent aortic valve. This is only the second known case of absent aortic valve in association with DiGeorge syndrome. We discuss the association of absent aortic valve with other conotruncal defects and the utility of fetal echocardiography in the diagnosis of DiGeorge syndrome.

MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma.

Recent identification of somatic MED12 mutations in most uterine leiomyomas brings a new venue for the study of the tumorigenesis of leiomyomas. We are particularly interested in the correlation of MED12 and HMGA2 gene products in leiomyomas and leiomyosarcomas with and without MED12 mutations. To address these issues, in this study we examined MED12 mutations in a large cohort of usual type leiomyomas (178 cases) and uterine leiomyosarcomas (32 cases). We found that 74.7% (133/178) of leiomyomas had MED12 mutations, which was consistent with several independent studies. In contrast, only 9.7% (3/32) of leiomyosarcomas harbored MED12 mutations. Expression analysis by western blot and immunohistochemistry revealed that those leiomyomas with complex MED12 mutations had significantly lower protein products than the matched myometrium. Interestingly, most leiomyosarcomas without MED12 mutations also had very low levels of MED12 expression in comparison to the matched myometrium. These findings suggest a potential functional role of MED12 in both benign and malignant uterine smooth muscle tumors. When we further examined HMGA2 expression in all leiomyomas and leiomyosarcomas, we found that HMGA2 overexpression was exclusively present in those leiomyomas with no MED12 mutation, accounting for 10.1% (18/178) of total leiomyomas and 40% (18/45) of non-MED12 mutant leiomyomas. Twenty-five percent (8/32) of leiomyosarcomas had HMGA2 overexpression, and no MED12 mutations were found in HMGA2 positive leiomyosarcoma. These findings strongly suggest that MED12 mutations and HMGA2 overexpression are independent genetic events that occur in leiomyomas, and they may act differently in the tumorigenesis of uterine leiomyomas.

Luminal subtypes predict improved survival following central nervous system metastasis in patients with surgically managed metastatic breast carcinoma.

CONTEXT: Metastatic breast cancer to the central nervous system (CNS) is second only to lung cancer metastasis to the CNS in frequency. Patients with triple-negative primary breast cancer and those with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer are at an increased risk for metastasis. Very little is known about predictive or prognostic variables once patients develop CNS metastases. Currently, therapeutic options are limited, with surgery generally offered primarily to those with solitary lesions. OBJECTIVES: To determine the influence of molecular subtypes of metastatic breast cancer on survival from the time of CNS metastasis and to aid in the prognostic stratification of these patients. DESIGN: We identified 59 cases of metastatic breast cancer to the CNS and analyzed them for various demographic and clinicopathologic parameters. Tumors were categorized into molecular subtypes using immunohistochemical methods: luminal A [estrogen receptor (ER⁺)/Ki67low], luminal B (ER⁺/Ki67 high), intrinsic HER2 (ER⁻/HER2⁺), and triple-negative. Survival after CNS metastasis for each group was plotted using a Kaplan-Meier curve, and multivariate analysis was performed. RESULTS: Patients with metastases from luminal tumors had a statistically significant survival advantage when compared with those of the triple-negative phenotype. Importantly, survival among patients with luminal A and luminal B tumors was not significantly different. Similarly, patient's age, histologic grade, and number of lesions did not contribute to determining outcomes. CONCLUSIONS: Estrogen receptor positivity (ie, luminal phenotype) of tumors appears to determine outcomes after development of metastases. In contrast, proliferation rate had little or no effect on the long-term survival. Understanding the biology of metastases can help stratify patients into prognostically meaningful categories and tailor treatment regimens for individual patients.

Polysomy of chromosomes 1 and/or 19 is common and associated with less favorable clinical outcome in oligodendrogliomas: fluorescent in situ hybridization analysis of 84 consecutive cases.

It is well established that the combined del(1)(p36) and del(19)(q13) is a positive prognostic molecular event in oligodendroglial tumors. However, very little is known about the frequency or impact of polysomy status for chromosomes 1/19. We examined 84consecutive pure oligodendrogliomas (68 World Health Organization [WHO] grade II and 16 WHO grade III) and analyzed them for del(1)(p36) and del(19)(q13) by fluorescent in situ hybridization. Polysomy status was recorded with accompanying deletion status, WHO grade, recurrence-free survival, and overall survival. Codeletion of 1p/19q was detected in 48% of cases and correlated with superior patient survival (p < 0.01), as expected. Of 84 cases, 36 (43%) showed polysomy of chromosome 1, 30 (36%) demonstrated polysomy of chromosome 19, and 28 (33%) had copolysomies of chromosomes 1/19. The presence of polysomy of either/or both chromosomes, regardless of deletion status, correlated with younger patient age at initial diagnosis (p < 0.01). Combined polysomy was associated with higher histologic tumor grade (p = 0.04) and conferred poor survival likelihood (p = 0.03). We conclude that polysomy of 1 and/or 19 is a relatively frequent occurrence in oligodendrogliomas and usually confers an unfavorable outcome.