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Andrology May 2013Seminoma and non-seminoma tumours increasingly occur within the western population. These tumours originate from carcinoma in situ (CIS) cells, which arise from...
Seminoma and non-seminoma tumours increasingly occur within the western population. These tumours originate from carcinoma in situ (CIS) cells, which arise from dysfunctional gonocytes. CXCL12 and its receptors, CXCR4 and CXCR7, have been implicated in migration, proliferation and survival of gonocytes and their precursors and progeny, primordial germ cells and spermatogonial stem cells respectively. We previously found evidence that several miRNA molecules predicted to modulate CXCR4 signalling are differentially expressed during the differentiation of gonocytes into spermatogonia in mice. Bioinformatic analysis predicted these miRNA to modulate CXCR4 signalling, leading us to hypothesize that CXCL12-mediated CXCR4 signalling is involved in the disrupted differentiation of gonocytes that underpins CIS formation. Indeed, we detected CXCL12 in Sertoli cells of normal human testis, and relatively high expression in tumour stroma with concomitant weak staining in dispersed tumour cells. In contrast, CXCR4 was expressed in spermatogonial and meiotic germ cells of normal testis and in the majority of tumour cells. Quantitative RT-PCR identified elevated CXCR4 transcript levels in seminoma compared with normal testis and to non-seminoma, potentially reflecting the higher proportion of dysfunctional germ cells within seminomas. In the normal testis, expression of CXCR4 downstream signalling molecules phospho-MEK1/2 and phospho-ERK1/2 correlated with CXCR4/CXCL12 expression. Strikingly, this correlation was absent in seminoma and non-seminoma samples, suggesting that CXCL12 signalling is disrupted. Proliferation rate and cell survival were not altered by CXCL12 in either seminoma (TCam-2) or non-seminoma (833ke) cell lines. However, CXCL12 exposure induced TCam-2 cell invasion though simulated basement membrane, while in contrast, we provide the novel evidence that CXCR4-expressing non-seminoma cell lines 833ke and NTera2/D1 do not invade in response to CXCL12. These findings indicate that CXCL12 expression in the human testis may selectively influence seminoma migration and metastasis, correlating with its importance in gonocyte and spermatogonial stem cell biology.
Topics: Cell Line, Tumor; Chemokine CXCL12; Humans; Male; Neoplasm Metastasis; Receptors, CXCR4; Seminoma
PubMed: 23495012
DOI: 10.1111/j.2047-2927.2013.00081.x -
Urologia Internationalis 2018Clinical characteristics of testicular germ cell tumours (GCTs) apparently change over time, and some vary geographically. The aim of this study is to document the...
INTRODUCTION
Clinical characteristics of testicular germ cell tumours (GCTs) apparently change over time, and some vary geographically. The aim of this study is to document the clinical profile of contemporary GCT patients.
PATIENTS AND METHODS
Four hundred twenty-two Caucasian GCT-patients treated in one German centre during 2000-2017, were analysed in terms of patient-age, laterality, histology, tumour-size, clinical stages (CS), pathological (pT)-stages and serum biomarker expression. The results were analysed descriptively and compared with the literature.
RESULTS
Median age was 36 years and 60.2% had seminoma. Βeta-human chorionic gonadotropin was expressed in 37.9% and alpha Fetoprotein in 25.6%. CS1 presenting stage was 66.6% of all GCT patients, 79.1% in seminoma, and 47.6% in nonseminoma. Tumour size was significantly associated with pT-stages and CS. Patients >50 years had significantly more seminoma (77.6%) than younger ones (57.9%). Comparison with literature data revealed a shifting towards higher age, lower CS, higher proportion of seminoma and striking differences of characteristics among geographic regions.
CONCLUSIONS
A typical contemporary clinical profile of testicular GCTs is presented in this study. Median age, relative incidence of seminoma and proportion of CS1 appear to be increasing over time. Striking differences among ethnic groups regarding the characteristics of GCT require further investigation.
Topics: Adult; Age Factors; Humans; Incidence; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Germ Cell and Embryonal; Prognosis; Retrospective Studies; Seminoma; Testicular Neoplasms; Treatment Outcome
PubMed: 29649815
DOI: 10.1159/000488284 -
International Journal of Radiation... Jul 2022Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the...
PURPOSE
Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy.
METHODS AND MATERIALS
Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse.
RESULTS
With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression.
CONCLUSIONS
Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy.
Topics: Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Febrile Neutropenia; Follow-Up Studies; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Orchiectomy; Retrospective Studies; Seminoma; Testicular Neoplasms
PubMed: 35461737
DOI: 10.1016/j.ijrobp.2022.03.021 -
Folia Histochemica Et Cytobiologica 2019Testicular tumors are heterogeneous group of neoplasms divided mainly into two types: seminomas and non-seminomas. Nucleolin (NCL) and nucleophosmin (NPM) are abundant...
INTRODUCTION
Testicular tumors are heterogeneous group of neoplasms divided mainly into two types: seminomas and non-seminomas. Nucleolin (NCL) and nucleophosmin (NPM) are abundant nucleolar proteins involved in many physiologic and pathologic processes including cancer. Their overexpression was found in many tumors but it was not studied in testicular cancer.
MATERIAL AND METHODS
The study was performed on tissue microarrays of 19 seminomas, 21 embryonal carcinomas and 11 yolk sac tumors. The expression of NCL and NPM was detected with monoclonal antibodies and visualized with EnVision FLEX/HRP technique. Immunohistochemical reactions were measured with Aperio ImageScope Software and analyzed as means of percentages of all immunopositive cells in three groups of reaction intensity, i.e. 3+, 2+, and 1+ as well as of H-score.
RESULTS
Seminomas showed higher expression of nucleolin indicated by higher H-score and higher percentage of positive cells than non-seminomas. The differences in subpopulations of NCL-positive cells were also found. Embryonal carcinomas and yolk sac tumors showed lower expression of NCL than seminomas indicated by H-score. The percentage of NCL-positive cells did not differ between embryonal carcinomas and seminomas while there were significant differences in subpopulations of cells. The percentage of NCL-positive cells in yolk sac tumors was lower than in seminomas. The results show different heterogeneity of subpopulations of NCL-positive cells in embryonal carcinomas and yolk sac tumors compared to seminomas. The analysis of nucleolin expression in embryonal carcinomas and yolk sac tumors showed no differences between these two tumor types. No differences in nucleophosmin expression between seminomas and non-seminomas were found.
CONCLUSIONS
The differences in the expression of nucleolin between two groups of germ cell testicular tumors found in the current study indicate a new aspect of biology of these neoplasms and require further studies on the role of nucleolin in germ cell tumorigenesis.
Topics: Adult; Cell Nucleus; Humans; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Nuclear Proteins; Nucleophosmin; Phosphoproteins; RNA-Binding Proteins; Seminoma; Testicular Neoplasms; Testis; Young Adult; Nucleolin
PubMed: 31513277
DOI: 10.5603/FHC.a2019.0015 -
Archives of Pathology & Laboratory... Apr 2008The histopathology of testicular tumors is presented, emphasizing new, unusual, or underemphasized aspects. Within the category of seminoma of the usual type, the recent... (Review)
Review
The histopathology of testicular tumors is presented, emphasizing new, unusual, or underemphasized aspects. Within the category of seminoma of the usual type, the recent literature has drawn attention to the presence in occasional tumors of solid or hollow tubules or spaces of varying sizes and shape that may result in cribriform or microcystic patterns, causing potential confusion with other neoplasms, most notably Sertoli cell tumor or yolk sac tumor. Although regions of typical neoplasia and awareness of this phenomenon usually will be diagnostic, immunohistochemistry may play a role in excluding Sertoli cell tumor or yolk sac tumor. Although immunohistochemistry can play an undoubted helpful role in this and selected other areas of testicular tumor evaluation, careful evaluation of the gross and routine microscopic features will solve the vast majority of diagnostic problems. An excellent review of immunohistochemistry in this area by R. E. Emerson, MD, and T. M. Ulbright, MD, is cited herein. Spermatocytic seminoma remains a crucial pitfall in diagnosis, and the pathologist must always be alert to the possible diagnosis when looking at a seminomatous neoplasm, particularly in an older patient, although about one third of these tumors occur in the usual seminoma age range. The embryonal carcinoma has a great diversity of patterns, which are briefly noted. The enigmatic and picturesque tumor, polyembryoma, which virtually never occurs in pure form but may be a confusing component of a variety of mixed germ cell tumors, is discussed and illustrated. The phenomenon of burnt-out germ cell neoplasia is also briefly noted and an excellent recent contribution is referred to. Within the sex cord-stromal family of neoplasms, recent contributions and elaborations of unusual morphologic features of Leydig cell tumors and Sertoli cell tumors are presented. Within the Leydig cell family, cyst formation, adipose metaplasia, calcification or ossification, and spindle cell patterns may be particularly confusing, and in the Sertoli cell family, a great array of patterns caused by differing admixtures of tubular, solid, and stromal components occur. The peculiar lesion, intratubular large cell hyalinizing Sertoli cell tumor, of young boys with Peutz-Jeghers syndrome, is briefly discussed. Some of the problems in the family of hematopoietic neoplasms are reviewed, these processes posing diverse problems in differential diagnosis and their correct recognition having crucial therapeutic implications. Although secondary tumors to the testis have not received the same attention in the literature as the similar phenomenon in the female gonad, remarkable examples of testicular spread of diverse neoplasms, usually carcinoma but rarely melanoma, are seen, and the pathologist should be alert to this possibility, particularly when examining an unusual morphology in an older patient. Finally, a few comments are made on the common paratesticular neoplasm, the adenomatoid tumor, highlighting its varied patterns and recent description of some of the issues that may arise when they undergo total or subtotal infarction.
Topics: Carcinoma, Embryonal; Diagnosis, Differential; Endodermal Sinus Tumor; Humans; Male; Neoplasms, Germ Cell and Embryonal; Pathology; Seminoma; Teratoma; Testicular Neoplasms
PubMed: 18384207
DOI: 10.5858/2008-132-548-TTNAAF -
Annals of Oncology : Official Journal... Oct 2013
Topics: Antineoplastic Agents; Europe; Follow-Up Studies; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Orchiectomy; Risk Assessment; Salvage Therapy; Seminoma; Testicular Neoplasms; Treatment Outcome
PubMed: 24078656
DOI: 10.1093/annonc/mdt304 -
Oncology (Williston Park, N.Y.) Jun 2014
Review
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Male; Neoplasm Recurrence, Local; Neoplasms, Germ Cell and Embryonal; Salvage Therapy; Seminoma
PubMed: 25134324
DOI: No ID Found -
Cell Proliferation Mar 2019CSE1L has been reported to be highly expressed in various tumours. Testicular germ cell tumours are common among young males, and seminoma is the major type. However,...
OBJECTIVES
CSE1L has been reported to be highly expressed in various tumours. Testicular germ cell tumours are common among young males, and seminoma is the major type. However, whether CSE1L has functions in the seminoma is unclear.
MATERIALS AND METHODS
The expression of CSE1L was detected by immunohistochemistry in seminoma tissues and non-tumour normal testis tissues from patients. CSE1L distribution during cell mitosis was determined by immunofluorescent staining with CSE1L, α-tubulin and γ-tubulin antibodies. The effects of Cse1L knockdown on cell proliferation and cell cycle progression were determined by Cell Counting Kit-8 assay, flow cytometry, PH3 staining and bromodeoxyuridine incorporation assay.
RESULTS
CSE1L was significantly enriched in the seminoma tissue compared with the non-tumour normal testis tissue. CSE1L also co-localized with α-tubulin in the cells with a potential to divide. In the seminoma cell line TCam-2, CSE1L was associated with the spindles and the centrosomes during cell division. The knockdown of CSE1L in TCam-2 cells attenuated the cells' proliferative capacity. Cell cycle assay revealed that the CSE1L-deficient cells were mainly arrested in the G0/G1 phase and moderately delayed in the G2/M phase. The proportion of cells with multipolar spindle and abnormal spindle geometry was obviously increased by CSE1L expression silencing in the TCam-2 cells.
CONCLUSIONS
Overall, these findings showed that CSE1L plays a pivotal role in maintaining cell proliferation and cell division in seminomas.
Topics: Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cellular Apoptosis Susceptibility Protein; Gene Deletion; Humans; Male; Mitosis; Seminoma; Testicular Neoplasms; Testis
PubMed: 30485574
DOI: 10.1111/cpr.12549 -
International Journal of Cancer Mar 2020Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumors. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic...
Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumors. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOX17 drives endodermal cell fate. However, seminomas lack expression of endoderm markers, but show features of pluripotency. Here, we use chromatin immunoprecipitation sequencing to report and compare the binding pattern of SOX17 in seminoma-like TCam-2 cells to SOX17 in somatic cells and SOX2 in EC-like 2102EP cells. In seminoma-like cells, SOX17 was detected at canonical (SOX2/OCT4), compressed (SOX17/OCT4) and noncomposite SOX motifs. SOX17 regulates TFAP2C, PRDM1 and PRDM14, thereby maintaining latent pluripotency and suppressing somatic differentiation. In contrast, in somatic cells canonical motifs are rarely bound by SOX17. In sum, only 12% of SOX17-binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is highly dynamic and cell type specific. Deletion of SOX17 in seminoma-like cells resulted in loss of pluripotency, marked by a reduction of OCT4 protein level and loss of alkaline phosphatase activity. Furthermore, we found that in EC-like cells SOX2 regulates pluripotency-associated genes, most likely by partnering with OCT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.
Topics: Animals; Carcinoma, Embryonal; Cell Differentiation; Cell Line, Tumor; Chromatin Immunoprecipitation Sequencing; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Neoplasms, Germ Cell and Embryonal; Positive Regulatory Domain I-Binding Factor 1; RNA-Binding Proteins; SOXB1 Transcription Factors; SOXF Transcription Factors; Seminoma; Testicular Neoplasms; Transcription Factor AP-2; Transcription Factors; Transcriptional Activation; Xenograft Model Antitumor Assays
PubMed: 31583686
DOI: 10.1002/ijc.32714 -
International Braz J Urol : Official... 2020To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum...
PURPOSE
To assess the relationship between testicular germ cell tumors (TGCT) and neutrophil to lymphocyte ratio (NLR) and to determine whether this ratio can be used as a serum tumor marker.
MATERIAL AND METHODS
Sixty-one patients with testicular germ cell tumors were included into the study. Patients were grouped as localized and non-localized. Histologically patients were categorized as seminoma and nonseminomatous germ cell tumors. Complete blood cell count was measured the day before surgery and at the postoperative 1st month. Preoperative and postoperative mean NLR values were compared.
RESULTS
Thirty-six patients (59%) had seminomas and 25 patients (41%) had nonseminomatous testicular cancer. Forty-five patients (73.8%) had localized and 16 patients (26.2%) had non-localized testicular cancer. There was a statistically significant difference between preoperative and postoperative mean NLR of the localized patients (p=0.001) but no such difference was detected for non-localized patients (p=0.576). Nineteen patients with localized seminomas had normal preoperative serum tumor markers. There was a significant difference between preoperative and postoperative mean NLR in this group of patients (p=0.010). Twenty-six patients with localized tumors had preoperative increased serum tumor markers which normalized after orchiectomy. Mean NLR of these patients significantly decreased from 3.10 ± 2.13 to 1.62 ± 0.59 postoperatively (p=0.010).
CONCLUSIONS
NLR appears to be a useful marker for TGCT. It is successful in predicting localized and non-localized disease in early postoperative period.
Topics: Adult; Aged; Biomarkers, Tumor; Humans; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Neutrophils; Orchiectomy; Postoperative Period; Preoperative Care; Reference Values; Reproducibility of Results; Retrospective Studies; Seminoma; Sensitivity and Specificity; Statistics, Nonparametric; Testicular Neoplasms; Young Adult
PubMed: 31851466
DOI: 10.1590/S1677-5538.IBJU.2019.0321