Ülkü Öner

The importance of genomic copy number changes in the prognosis of glioblastoma multiforme

Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the progression of glioblastoma.

Genomic alterations in low-grade, anaplastic astrocytomas and glioblastomas.

To extend our understanding of potential stepwise genetic alterations that may underlie tumor progression from low-grade astrocytomas to glioblastomas, histopathologic and comparative genomic hybridization analyses were performed on tumor specimens from 68 primary lesions, including 40 glioblastomas, 10 anaplastic and 18 low-grade astrocytomas. The number of aberrations per case increased towards the higher grade tumors (grade II: 1.66±1.49; grade III: 2.80±1.68; grade IV: 3.02±1.07; F=6.955, p=0.002). A gain of 7/7q was common and the most frequently seen aberration in low-grade astrocytomas, whereas loss of 10q was the most frequently seen anomaly in anaplastic astrocytomas and glioblastomas. Chromosome 7p amplification was only detected in glioblastomas. Chromosome 10/10q deletion and combination of lp, 19q and 17p deletions were specific to high-grade astrocytic tumors. Sequences of chromosome 7 and 10 seem to have pivotal roles in the biology of human gliomas. The genomic copy deletions of chromosomes lp and 19q might provide an alternative mechanism in the genesis of astrocytomas.

Epithelioid angiomyolipoma of the kidney

Abstract  Epithelioid angiomyolipoma is a recently recognized variant of angiomyolipoma, which is characterized by the presence of polygonal cells with densely eosinophilic cytoplasm and varying degrees of nuclear atypia. Only a relatively small number of cases of epithelioid angiomyolipoma of the kidney have been reported in the literature. We report a case of epithelioid angiomyolipoma of the kidney that occurred in a 38‐year‐old woman. The tumor was composed of diffuse sheets of epithelioid cells, adipocytes and only scattered thick‐walled blood vessels. The epithelioid cells had pleomorphic and hyperchromatic nuclei with densely eosinophilic cytoplasm. Hemorrhage, necrotic foci and clusters of foamy macrophages were present. HMB‐45, CD117 (c‐kit) and CD68 were detected in the epithelioid cells. There was no expression of cytokeratin, epithelial membrane antigen or desmin. The patient showed no evidence of recurrence or metastatic disease 9 months after nephrectomy.

Differential expression of P16 and P21 in benign and malignant uterine smooth muscle tumors

PurposeThe diagnosis of benign and malignant uterine smooth muscle tumors depends on morphologic criteria such as nuclear atypia, coagulative tumor cell necrosis and mitotic activity. Most of these tumors are readily classifiable into benign or malignant categories using these criteria. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. Hence, it would be useful to have additional markers which could help to distinguish these tumors. The aim of the study was to evaluate p16 and p21 expressions in uterine smooth muscle tumors and determine whether p16 and p21 have a potential value in the differential diagnosis of problematic cases. In addition, we evaluated whether the differential expression of p16 and p21 in uterine leiomyosarcomas correlated with tumor recurrence and patient survival.Methodsp16 and p21 expressions were investigated by immunohistochemistry from paraffin-embedded tissues in 53 cases of uterine smooth muscle tumors consisting of 15 cases of leiomyoma, 14 cases of atypical leiomyoma (leiomyoma with bizarre nuclei), 3 cases of smooth muscle tumor of uncertain malignant potential (STUMP) and 21 cases of leiomyosarcoma. Cases were evaluated with respect to both staining percentage and intensity.ResultsThere was a statistically significant difference in p16 and p21 staining percentage and intensity between leiomyosarcomas and the other groups. There was no difference in p16 and p21 expressions between leiomyomas, atypical leiomyomas (leiomyoma with bizarre nuclei) and STUMPs. Multivariate analysis showed that the tumor stage was the only independent significant prognostic factor for overall survival in leiomyosarcomas. Neither p16 nor p21 was correlated with disease-free or overall survival.ConclusionsOur findings suggested that p16 and p21 may be of value as an adjunct to conventional morphologic criteria in the assessment of problematic uterine smooth muscle tumors.

Burned-out tumor of the testis presenting as supraclavicular lymphadenopathy

Abstract. Burned-out tumor of the testis is a rare clinical entity. It generally presents with metastases and is nonpalpable in testicular palpation. We present a case of testicular burned-out tumor having supraclavicular and retroperitoneal lymph node metastases. Imaging findings of such tumors have insufficiently been documented in radiology literature. Scrotal sonography is crucial in detecting the regressed tumors especially in patients with extragonadal metastasis of a testicular primary.

Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treated by total laryngectomy

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in laryngeal squamous cell carcinomas. Ki-67 labeling was quantified in 63 laryngeal squamous cell carcinomas by counting at least 1,000 tumor cells in the most immunoreactive area in each sample, and the Ki-67 labeling index was calculated as a percentage. The antigen expression was compared with clinical factors, histopathological grading and prognosis. The Ki-67 mean proliferation index for all patients was 25.44% ( range, 2–75%). A significant correlation was found between Ki-67 mean proliferation index and patient age (P<0.05), T-stage (P<0.05), nodal metastasis (P=0.001) and recurrence (P<0.001). There was no significant association between the Ki-67 mean proliferation index and tumor site or histologic grade. A univariate analysis showed that the Ki-67 labeling index >21% (P<0.001), T-stage (P<0.001) and nodal metastasis (P=0.001) are determinants of recurrence. In the multivariate analysis, the Ki-67 labeling index >21% (P<0.001), T-stage (P<0.001) and nodal metastasis (P<0.05) were independent predictors of recurrence. Kaplan-Meier plots of survival in patients with Ki-67 values above and below the median (21%) of the general study population showed that a high Ki-67 labeling index correlated with a shorter disease-free survival (P<0.0001). The analysis of the Ki-67 labeling index at the time of initial surgery may be a powerful prognostic marker for patients with laryngeal squamous cell carcinoma and may be useful for selecting subgroups of patients who should be treated with more aggressive therapies.

BCL2, BCL6, IGH, TP53, and MYC protein expression and gene rearrangements as prognostic markers in diffuse large B-cell lymphoma: a study of 44 Turkish patients.

The purpose of this study was to determine the frequency of BCL2, BCL6, IGH, TP53, and MYC protein expression and rearrangements of the respective genes in diffuse large B-cell lymphoma (DLBCL) patients and to assess their prognostic values. Samples from 44 patients with DLBCL were evaluated using fluorescence in situ hybridization and immunohistochemical analyses. BCL6 was the most rearranged gene (63.6%), followed by MYC (31.8%), TP53 (22.7%), and BCL2 (18.2%). Multiple rearrangements were detected in 40.9% of the cases. BCL6 was the most expressed protein (78.6%), followed by TP53 (69.04%), BCL2 (59.5%) and MYC (14.3%). Expression of multiple proteins was detected in 67.4% of the cases. BCL2 (P = .003) expression had a significant negative influence on overall survival,whereas BCL6 (P = .014) expression had a significant positive influence. Our results with a different pattern of gene rearrangements and associated protein overexpression indicate the molecular genetic complexity of DLBCLs, which reflects the morphologic, biologic, and clinical heterogeneity of these lymphomas.

An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.