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Background: The authors evaluated the utility of immunofluorescence staining with an antipromyelocytic leukemia (anti-PML) antibody for patients with a suspected diagnosis of new or relapsed acute promyelocytic leukemia (APL) and correlated the findings with the results of other established diagnostic modalities.Methods: Bone marrow (BM) and/or peripheral blood (PB) smears from 349 patients in whom the diagnosis of APL was considered were assessed with the anti-PML antibody using immunofluorescence. The study group included 199 patients with confirmed APL and 150 with other conditions. The results of conventional cytogenetics, reverse transcription polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH) performed on these patients were correlated with the PML results.Results: Among patients with confirmed APL, anti-PML antibody was positive in 182 of 184 BM and 32 of 33 PB smears. Conventional cytogenetics demonstrated t(15;17)(q22;q12) in 166 of 182 (91%) patients; 10 had a normal karyotype, 4 had insufficient mitoses to grow in culture, 1 was inconclusive, and 1 was 48, XX, +8, +8. Anti-PML staining was positive in 9 of 10 with a normal karyotype and in all 4 cases with insufficient mitoses. RT-PCR and FISH were positive for PML-retinoic acid receptor-alpha in 169 of 172 (98%) and 90 of 94 (96%) cases, respectively. Among the patients without APL, 148 of 150 (98.6%) were negative with anti-PML antibody. The sensitivity and specificity of the test were 98.9% and 98.7%, respectively.Conclusions: PML immunofluorescence staining is a rapid (<4 hours turnaround time) and reliable frontline diagnostic approach that can facilitate initiation of targeted therapy, particularly in clinical settings where cytogenetic and molecular testing are not readily available. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed 1792 consecutive radical prostatectomies (RP) from 2003 to 2006 at a single institution to establish tumor volume reference values, to determine current trends in visually estimated prostate adenocarcinoma tumor volume, and to characterize cases with no residual cancer on RP. Tumor volumes were recorded and subsequently stratified as very low, 0-1%; low, 1.1-10%; intermediate, 10.1-20%; high, 20.1-50%; and very high, >50%, with incidences of 11.7%, 52.1%, 21.5%, 13.2%, and 1.5%, respectively. The incidence of very low volume tumors increased within the time period (p=0.04). Seminal vesicle involvement was detected in 5.0% of cases and lymph node metastasis occurred in 1.4%. Volume categories statistically correlated with seminal vesicle invasion (p=0) and lymph nodes metastases (p=0). Eleven cases of no residual cancer (0.6%) were identified with a non-statically significant increase during the study (p=0.07). The rising incidence of very low volume tumors should be considered by clinicians when discussing treatment options with patients. A discrete tumor volume should be provided for RP specimens as it may be an important prognostic factor., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Despite the success of the current therapy for patients with acute promyelocytic leukemia (APL), relapse occurs in up to 30% of patients. The characteristics of relapsed APL are not well described. We evaluated a group of APL cases at relapse and compared the clinicopathologic, immunophenotypic, molecular, and cytogenetic findings with those at initial diagnosis. From a group of 207 patients with APL, in 38 patients morphologic evidence of relapse developed. In 30 patients relapse was isolated to bone marrow, and 8 had extramedullary disease. Blasts were morphologically stable in 37 patients. Changes in the immunophenotypic profile were common, the most frequent being gain of CD34, HLA-DR, or CD33 and attenuation or loss of CD13. Cytogenetic changes were common at relapse. The size of the PML-RARalpha fusion transcript was invariable. We conclude that changes in the immunophenotype and cytogenetic evidence of clonal evolution are common in APL at the time of relapse.

Germ cell tumors (GCTs), rare malignancies that occur in a wide range of locations and display variable histologic patterns, may pose diagnostic challenges. Glypican 3 (GPC3), a membrane-bound heparan sulfate proteoglycan, has been shown to be a novel diagnostic marker in testicular GCT. However, GPC3 expression in ovarian and extragonadal GCT has not been reported. We evaluated GPC3 immunoreactivity in GCTs from 63 patients (57 children and 6 adults), including 14 ovarian and 20 extragonadal primary GCTs and 8 metastases along with 21 primary testicular GCTs for comparison. All 33 yolk sac tumors (YSTs) and both choriocarcinomas were immunoreactive for GPC3. In contrast, a minority of immature (4/10) and mature (4/35) teratomas were positive. No positivity was seen in 6 embryonal carcinomas or 5 germinomas. GPC3 is differentially expressed in ovarian and extragonadal GCTs, with expression predominantly observed in YSTs and choriocarcinoma.

Aims: Neural (N)-cadherin belongs to a group of transmembrane molecules with a crucial role in tissue morphogenesis and maintenance of an epithelioid phenotype and increased N-cadherin expression is implicated in tumour progression and dedifferentiation. The aim was to determine whether evaluation of N-cadherin in pulmonary tumours might assist in identifying lesions with more aggressive potential., Methods and Results: One hundred and fifty-five pulmonary lesions were analysed for N-cadherin expression using immunohistochemistry, including neuroendocrine hyperplasia (n = 3), typical carcinoid (n = 59), atypical carcinoid (n = 12), small cell lung carcinoma (n = 11), large cell neuroendocrine carcinoma (n = 12), adenocarcinoma (n = 35) and squamous cell carcinoma (n = 23). Lymph node status was correlated with immunohistochemical expression. N-cadherin expression was demonstrated in all cases of neuroendocrine hyperplasia, 96% of typical carcinoids, 83% of atypical carcinoids, 63% of the small cell lung carcinomas and 32% of large cell neuroendocrine carcinomas. Over 90% of the adenocarcinomas and 100% of the squamous cell carcinomas were negative. Increased N-cadherin expression in typical carcinoids was associated with negative lymph node status (P < 0.001)., Discussion: N-cadherin is differentially expressed in pulmonary tumours and is predominantly observed in neuroendocrine lung lesions with high expression in typical and atypical pulmonary carcinoids. The level of expression of N-cadherin between types of lung tumours does not appear to indicate malignant potential or aggressive behaviour.

Objectives: Inhibitors of topoisomerase II alpha (TopoIIalpha), an enzyme with a crucial role in DNA maintenance, are included in the chemotherapy protocols for testicular germ cell tumors (GCTs). Despite the success of current chemotherapy regimens, a significant number of patients experience relapse. We analyzed TopoIIalpha expression in primary and metastatic testicular GCTs because this enzyme is a target for some antineoplastic agents., Methods: Primary GCT specimens from 109 patients, including 57 seminomas and 52 mixed GCTs (41 embryonal carcinomas, 23 yolk sac tumors, 19 seminomas, 8 choriocarcinomas, 17 teratomas with immature elements, and 16 teratomas with mature elements), were obtained from our archives. The metastatic lesions from 11 of the patients with mixed GCTs included seven teratomas with mature components, five embryonal carcinomas, one yolk sac tumor, one choriocarcinoma, and one teratoma with immature components. Representative sections were subjected to immunohistochemistry with monoclonal antibody against TopoIIalpha, and the nuclear staining findings were evaluated., Results: Most embryonal carcinoma (100%), yolk sac tumor (95%), seminoma (88%), and choriocarcinoma (62%) components of the GCTs were TopoIIalpha immunoreactive. None of the teratoma specimens with mature elements expressed TopoIIalpha., Conclusions: The results of our study have shown that TopoIIalpha is expressed in most seminomas, embryonal carcinomas, yolk sac tumors, and choriocarcinomas, suggesting a possible mechanism of sensitivity of these components to TopoIIalpha inhibitors. Teratomas with mature and immature elements expressed low levels of TopoIIalpha, which might contribute to their chemoresistance. These findings imply that the variable chemoresponsiveness of testicular GCTs could have an underlying molecular basis.

Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). We conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Our findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma.