Testicular cancer seminoma is one of the most common types of cancer among men of reproductive age. Patients with this condition usually present reduced semen quality, even before initiating cancer therapy. However, the underlying mechanisms by which testicular cancer seminoma affects male fertility are largely unknown. The aim of this study was to investigate alterations in the sperm proteome of men with seminoma undergoing sperm banking before starting cancer therapy, in comparison to healthy proven fertile men (control group). A routine semen analysis was conducted before cryopreservation of the samples (n = 15 per group). Men with seminoma showed a decrease in sperm motility (P = 0.019), total motile count (P = 0.001), concentration (P = 0.003), and total sperm count (P = 0.001). Quantitative proteomic analysis identified 393 differentially expressed proteins between the study groups. Ten proteins involved in spermatogenesis, sperm function, binding of sperm to the oocyte, and fertilization were selected for validation by western blot. We confirmed the underexpression of heat shock-related 70 kDa protein 2 (P = 0.041), ubiquinol-cytochrome C reductase core protein 2 (P = 0.026), and testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (P = 0.016), as well as the overexpression of angiotensin I converting enzyme (P = 0.005) in the seminoma group. The altered expression levels of these proteins are associated with spermatogenesis dysfunction, reduced sperm kinematics and motility, failure in capacitation and fertilization. The findings of this study may explain the decrease in the fertilizing ability of men with seminoma before starting cancer therapy.
Acrosin/metabolism* ; Adult ; Case-Control Studies ; Chaperonin Containing TCP-1/metabolism* ; Electron Transport Complex III/metabolism* ; HSP70 Heat-Shock Proteins/metabolism* ; Humans ; Male ; Peptidyl-Dipeptidase A/metabolism* ; Proteasome Endopeptidase Complex/metabolism* ; Proteomics ; Semen Analysis ; Seminoma/metabolism* ; Sodium-Potassium-Exchanging ATPase/metabolism* ; Sperm Count ; Sperm Motility ; Spermatozoa/metabolism* ; Testicular Neoplasms/metabolism*

ObjectiveTo study the pathological morphology, immunohistochemical characteristics, and molecular changes of type Ⅱ testicular germ cell tumors (TGCT) and investigate the possible value of immunohistochemistry and fluorescence in situ hybridization (FISH) in the diagnosis of TGCT.

METHODSWe collected for this study 97 cases of TGCT, including 75 cases of seminoma, 17 cases of embryonal carcinoma, 11 cases of yolk sac tumor, 16 cases of mature teratoma, 3 cases of immature teratoma, and 1 case of epidermoid cyst, in which normal testicular tissue was found in 20 and non-TGCT in 6. We detected the expressions of different antibodies in various subtypes of TGCT by immunohistochemistry and determined the rate of chromosome 12p abnormality using FISH.

RESULTSThe immunophenotypes varied with different subtypes of TGCT. SALL4 and PLAP exhibited high sensitivity in all histological subtypes. CD117 and OCT4 showed strongly positive expressions in invasive seminoma and germ cell neoplasia in situ (GCNIS) but not in normal seminiferous tubules. GPC3 was significantly expressed in the yolk sac tumor, superior to GATA3 and AFP in both range and intensity. CKpan, OCT4, and CD30 were extensively expressed in embryonal carcinoma, while HCG expressed in choriocarcinoma. The positivity rate of isochromosome 12p and 12p amplification in TGCT was 96.7% (29/30).

CONCLUSIONSThe majority of TGCT can be diagnosed by histological observation, but immunohistochemical staining is crucial for more accurate subtypes and valuable for selection of individualized treatment options and evaluation of prognosis. Chromosome 12p abnormality is a specific molecular alteration in type Ⅱ TGCT, which is useful for ruling out other lesions.

Biomarkers, Tumor ; metabolism ; Carcinoma, Embryonal ; diagnosis ; genetics ; metabolism ; pathology ; Chromosome Aberrations ; Chromosomes, Human, Pair 12 ; Endodermal Sinus Tumor ; diagnosis ; genetics ; metabolism ; pathology ; Genetic Markers ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; genetics ; metabolism ; pathology ; Prognosis ; Seminiferous Tubules ; metabolism ; Seminoma ; diagnosis ; genetics ; metabolism ; pathology ; Teratoma ; diagnosis ; genetics ; metabolism ; pathology ; Testicular Neoplasms ; diagnosis ; genetics ; metabolism ; pathology

OBJECTIVETo analyze the clinicopathologic and immunohistochemical features of nodular histiocytic/mesothelial hyperplasia (NHMH) and to improve the knowledge of this disease.

METHODSSeven cases of NHMH were collected and the clinicopathologic and immunohistochemical data were analyzed with review of the literature.

RESULTSSeven male patients aged from 1.5 to 5.0 years (mean 2.8). The main clinical symptom was an inguinal mass.Grossly, main pathological changes were the mural nodule or free nodule in lumen, with diameter of 0.1-0.5 cm.Histologically, the tumor cell morphology was relatively single, cohesive polygonal or oval cells which were arranged in solid sheets or nests, usually with ovoid or deeply grooved nuclei and a moderate amount of pale pink cytoplasm in the nodular collection area. The nuclei had delicate chromatin and no obvious atypia, and mitosis was incidentally found. A few scattered lymphocytes were found in the stroma. The cyst wall was lined by a single layer of mesothelial cells.Immunohistochemically, the most cells in nodular lesion were strongly positive for the histiocytic marker CD68, vimentin and α1-antichymotrypsin, while lining mesothelial cells on the wall were positive for calretinin, MC, WT1, CK5/6, CKpan and EMA.

CONCLUSIONSNHMH is a rare and benign tumor-like lesion, and easy to be misdiagnozed, which should be distinguished from neuroendocrine tumors, Langerhans cell histiocytosis, seminoma, mesothelioma and so on. The correct diagnosis of this lesion depends on the clinical characteristics, morphology and immunohistochemistry.

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Calbindin 2 ; metabolism ; Child, Preschool ; Diagnosis, Differential ; Epithelium ; metabolism ; pathology ; surgery ; Histiocytes ; metabolism ; pathology ; Histiocytosis, Langerhans-Cell ; metabolism ; pathology ; Humans ; Hyperplasia ; metabolism ; pathology ; surgery ; Infant ; Leukocyte Common Antigens ; metabolism ; Male ; Mesothelioma ; metabolism ; pathology ; Mucin-1 ; metabolism ; Neuroendocrine Tumors ; metabolism ; pathology ; Seminoma ; metabolism ; pathology ; Vimentin ; metabolism ; WT1 Proteins ; metabolism ; alpha 1-Antichymotrypsin ; metabolism

Adenoma ; metabolism ; pathology ; Adult ; Alkaline Phosphatase ; metabolism ; Antibodies, Monoclonal, Murine-Derived ; metabolism ; Diagnosis, Differential ; Ear Canal ; Ear Neoplasms ; metabolism ; pathology ; radiotherapy ; surgery ; GPI-Linked Proteins ; metabolism ; Humans ; Isoenzymes ; metabolism ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Mast-Cell Sarcoma ; metabolism ; pathology ; Proto-Oncogene Proteins c-kit ; metabolism ; Seminoma ; metabolism ; pathology ; radiotherapy ; surgery ; Vimentin ; metabolism ; Young Adult

Adult ; Antigens, CD20 ; metabolism ; Carcinoma ; metabolism ; pathology ; DNA Nucleotidylexotransferase ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratins ; metabolism ; Lymphoma ; metabolism ; pathology ; Male ; Middle Aged ; Necrosis ; Seminoma ; metabolism ; pathology ; Thymoma ; metabolism ; pathology ; surgery ; Thymus Neoplasms ; metabolism ; pathology ; surgery ; Tuberculosis ; pathology

OBJECTIVETo study the clinicopathologic features and biological behavior of spermatocytic seminoma.

METHODSA retrospective analysis of patients diagnosed as seminoma, spermatocytic seminoma between January 2003 and May 2011, was performed. Clinical data, HE stained section and immunohistochemical staining (SP method) were reviewed with follow-up.

RESULTSSixty-six cases of seminoma and 5 cases of spermatocytic seminoma were identified. The average age at the diagnosis of 5 cases of spermatocytic seminoma was 53 years, and no patient had a history of crytorchidism or germ cell tumor. All five patients had stage pT1 tumor. Immunohistochemical studies showed that spermatocytic seminoma was negative for CK, vimentin, OCT3/4, PLAP, and LCA, and PAS staining was also negative. All five patients were well after operation. In contrast, the average age at diagnosis of the 66 cases of seminoma was 37 years, in which 12% had a history of crytorchidism and 11% were in stage pT2 or the above. Immunohistochemical studies showed that seminoma was positive for OCT3/4, PLAP, and CD117. During the follow-up, 2 patients developed metastasis and 3 patients died of the disease.

CONCLUSIONSSpermatocytic seminoma is rare and appears to follow a benign clinical course Due to its favourable prognosis, further treatment is not necessary after orchidectomy. Accurate pathologic diagnosis is critical for patient management and for avoiding over-treatment.

Adult ; Aged ; Alkaline Phosphatase ; metabolism ; Diagnosis, Differential ; Follow-Up Studies ; GPI-Linked Proteins ; metabolism ; Humans ; Isoenzymes ; metabolism ; Male ; Middle Aged ; Neoplasm Staging ; Octamer Transcription Factor-3 ; metabolism ; Orchiectomy ; Proto-Oncogene Proteins c-kit ; metabolism ; Retrospective Studies ; Seminoma ; metabolism ; pathology ; surgery ; Spermatocytes ; pathology ; Testicular Neoplasms ; metabolism ; pathology ; surgery

OBJECTIVETo understand the role of the JAK/STAT3 signal transduction pathway in the pathogenesis of seminoma by studying the expressions of signal transducers and activators of transcription-3 (STAT3), vascular endothelial growth factor (VEGF) and C-myc in seminoma.

METHODSWe examined 38 paraffin specimens of seminoma and 10 samples of normal human testes by immunohistochemical staining using the antibodies of STAT3, VEGF and C-myc, and observed the staining intensity under the light microscope.

RESULTSThe positive expression rates of STAT3, VEGF and C-myc were 76.3%, 71.1% and 84.2%, respectively, with statistically significant differences from the corresponding protein expressions in the normal testis tissues (P < 0.01), which gradually increased with the clinical stages of tumor, nodes and metastasis (TNM) classification. Different correlations were observed among the STAT3, VEGF and C-myc proteins in seminoma: STAT3 positively correlated with VEGF (r = 0.640, P < 0.01) and C-myc (r = 0.408, P < 0.05); C-myc positively correlated with VEGF (r = 0.459, P < 0.01).

CONCLUSIONThe JAK/STAT3 signal transduction pathway can facilitate the development and metastasis of seminoma by activating the expression of VEGF and meanwhile induce the malignant proliferation of primary reproductive cells and promote the pathogenesis and progression of seminoma by activating the expression of C-myc.

Adult ; Aged ; Humans ; Janus Kinases ; physiology ; Male ; Middle Aged ; Neoplasm Staging ; Proto-Oncogene Proteins c-myc ; biosynthesis ; STAT3 Transcription Factor ; biosynthesis ; Seminoma ; metabolism ; pathology ; Signal Transduction ; Testicular Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; biosynthesis

Primary testicular tumors are the most common causes of cancer in male dogs. Overall, the majority of canine patients should be cured by testicular surgery. However, tumor markers are not well-known in veterinary medicine. We sought to determine using immunohistochemistry whether the combined human testicular tumor markers (placental alkaline phosphatase, OCT3/4, CD30, alpha-fetoprotein, inhibin-alpha, vimentin, c-KIT, and desmin) are expressed in canine seminomas and Sertoli cell tumors (SCTs). We examined 35 canine testicular tumors, 20 seminomas and 15 SCTs. c-KIT was expressed markedly in canine seminomas. Both inhibin-alpha and vimentin were expressed significantly in canine SCTs. The results of this study demonstrate differences and similarities between tumor marker expression of testicular tumors in dogs and humans. All the main markers in current routine use are discussed as well as potential useful markers for benign and malignant tumors, and tumor progression.
Animals ; Dog Diseases/*pathology ; Dogs ; Immunohistochemistry/*veterinary ; Male ; Seminoma/metabolism/pathology/*veterinary ; Sertoli Cell Tumor/metabolism/pathology/*veterinary ; Tumor Markers, Biological/metabolism

OBJECTIVETo evaluate the expression of CD117 in human testicular germ cell tumors and its value in the differential diagnosis of seminoma and nonseminoma.

METHODSSeventy-four human testicular germ cell tumor specimens were studied by ABC kit immunohistochemical staining detection using CD117 monoclonal antibodies. The immunoreaction scores (IRS) of all the specimens were calculated and analysed for their clinical significance.

RESULTSAmong the 74 germ cell tumors, 31 out of 32 (9 6.9%) seminomas showed positive staining of the CD117 mostly on the cell membrane. Four of 31 (12.9%) nonseminomas displayed a weak positive staining of CD117 only in the cytoplasm of a few cells. In 10 of 11 mixed germ cell tumors, a relatively weak expression of CD117 was shown only in the seminoma component. The CD117 expression was diagnostically decreased from seminoma to mixed seminoma and to nonseminoma successively, with IRS of 6.82 +/- 2.76, 1.25 +/- 0.42 and 0.60 +/- 0.16, respectively. There was a significant difference in the CD117 expression between seminoma and nonseminoma (P < 0.05). CD 117 proteins were positively expressed in all the 20 specimens of the normal testis.

CONCLUSIONThe detection of CD117 by immunohistochemical staining using CD117 monoclonal antibodies is a newly developed useful method for differentiating seminoma and nonseminoma.

Adolescent ; Adult ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Male ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; metabolism ; Predictive Value of Tests ; Proto-Oncogene Proteins c-kit ; biosynthesis ; Seminoma ; diagnosis ; metabolism ; Testicular Neoplasms ; diagnosis ; metabolism

OBJECTIVETo study the clinicopathologic features, immunohistochemical findings and prognosis of primary diffuse large B-cell lymphoma (DLBCL) of testis.

METHODSFourteen cases of primary DLBCL of testis, diagnosed according to the 2001 World Health Organization staging standards for hematopoietic and lymphoid tumors, were retrospectively studied. Immunohistochemical study was performed and follow-up information analyzed.

RESULTSThe median age of the patients was 62 years. There were 10 patients in stage I, 3 in stage II and 1 in stage IV. Follow-up information was available in 11 patients (78.6%). Three of which were still alive and eight died (with duration of survival ranging from 5 to 19 months). The patients usually presented with unilateral painless enlargement of testis. Histologically, the lymphoma cells of all cases showed a centroblastic appearance. One case belonged to the germinal center B cell-like subtype on immunohistochemical study, while the remaining 13 cases were classified as non-germinal center B cell-like subtype. Ten of the 14 cases (71.4%) showed overexpression of p53 protein. Most cases demonstrated high proliferation index. Six of the 14 cases (42.9%) were positive for bcl-2 protein. The overall 1-year, 2-year and 5-year survival rates were 45.5%, 17.0% and 17.0%, respectively.

CONCLUSIONSMost cases with primary DLBCL of testis were of peripheral activated B-cell origin. The prognosis is usually not favorable, with propensity of local relapse and systemic dissemination. Accurate pathologic diagnosis relies on detailed histologic examination and immunohistochemical study.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Germinoma ; drug therapy ; metabolism ; pathology ; surgery ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neprilysin ; metabolism ; Orchiectomy ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Retrospective Studies ; Seminoma ; pathology ; Survival Rate ; Testicular Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Tumor Suppressor Protein p53 ; metabolism ; Vincristine ; therapeutic use