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International Journal of Molecular... Jun 2022Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify...
Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (, , , , , , and ) related to metastatic disease. A significant association was found between increased expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA-miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA-miRNA regulation during disease progression.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Male; MicroRNAs; Penile Neoplasms; RNA, Messenger
PubMed: 35806108
DOI: 10.3390/ijms23137103 -
Modern Pathology : An Official Journal... Sep 2009Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and...
Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16(INK4A) and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16(INK4A) and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16(INK4A) and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16(INK4A) expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Verrucous; Cell Cycle Proteins; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Papillomavirus Infections; Penile Neoplasms; Polymerase Chain Reaction; Retinoblastoma Protein; Retrospective Studies; Tumor Suppressor Protein p53
PubMed: 19465901
DOI: 10.1038/modpathol.2009.77 -
Annals of Oncology : Official Journal... Nov 1997Penile carcinoma is uncommon in Western countries. Here we report on a large series of patients with squamous cell carcinoma (SCC) of the penis, describing prognostic...
BACKGROUND
Penile carcinoma is uncommon in Western countries. Here we report on a large series of patients with squamous cell carcinoma (SCC) of the penis, describing prognostic factors, survival and therapeutic results.
PATIENTS AND METHODS
From 1973 to 1993, 102 patients with invasive SCC of the penis were treated at the Institut Gustave-Roussy. Precancerous lesions and conditions associated with penis cancer were analyzed retrospectively. Survival curves were estimated by the Kaplan-Meier method, and groups were compared for outcome by the log rank test for univariate comparisons and by Cox's proportional hazards model for multivariate analysis.
RESULTS
The median age at onset was 58 years. Sixty-nine patients presented with Jackson's stage I disease, 17 with stage II and 15 with stage III. The interval between the manifestation of symptoms and the diagnosis was more than a year in 13.7% of cases. Precancerous lesions were found in 17 (16.6%) patients, and a history of phimosis was noted in 25 (24.5%). In situ and invasive carcinoma were observed together in 17 (16.6%) cases and dysplasia was associated with invasive carcinoma in eight (7.8%) further cases. Conservative treatment was administered whenever feasible. Interstitial brachytherapy was performed alone or associated with limited surgery (local excision or circumcision) in 72 (70.6%) patients. Of the 28 patients with a local relapse, nine have died of their neoplasms (32%) compared to 21 of 28 patients with lymph node relapse (75%). The median follow-up was 111 months. Disease-free survival, disease-specific survival and overall survival were, respectively, 56%, 72% and 63% at five years and 42%, 66% and 50% at 10 years. Age (P = 0.01), the N status (P < 0.00001) or palpable nodes (P < 0.0038), corpus involvement (P = 0.006) and a verrucous histology (P = 0.038) had significant prognostic relevance for survival in the univariate analysis whereas the performance status, T status and Broders' grade did not. In the multivariate analysis only two parameters, involvement of the corpus (P < 0.0001) and palpable nodes (P = 0.009), were singled out as being independent variables influencing survival. A subgroup of nine patients with verrucous histologies were distinguished by their freedom from node involvement. These patients had an excellent prognosis: all are alive and disease-free. Penile integrity was preserved during follow-up in 54 patients (52.9%), 31 of whom are still alive. Of 72 patients treated by a conservative approach including brachytherapy, long-term penile integrity was maintained in 49 (68%).
CONCLUSION
Corpus involvement and clinically palpable nodes are highly statistically significant independent factors influencing overall survival. Node relapses remain a major cause of death. Thus, better management of lymph nodes is essential for improving survival even when conservative therapy is used to treat the primary.
Topics: Adult; Aged; Aged, 80 and over; Brachytherapy; Carcinoma, Squamous Cell; Combined Modality Therapy; Disease-Free Survival; Humans; Male; Middle Aged; Multivariate Analysis; Penile Neoplasms; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 9426328
DOI: 10.1023/a:1008248319036 -
The Indian Journal of Surgery Aug 2014Sarcomatoid carcinoma or carcinosarcoma of the penis is a rare entity with 36 cases reported in the literature. A 61-year-old male presented with swelling in the glans...
Sarcomatoid carcinoma or carcinosarcoma of the penis is a rare entity with 36 cases reported in the literature. A 61-year-old male presented with swelling in the glans and shaft of the penis with bilateral inguinal lymph node metastases. He underwent total penectomy with bilateral inguinal block dissection. Histopathology revealed sarcomatoid carcinoma of the Penis with bilateral inguinal lymph node metastases. The patient later developed bilateral lung metastases in 6 months and was succumbed to death. Sarcomatoid carcinoma or carcinosarcoma is a rare malignancy with poor prognosis.
PubMed: 25278657
DOI: 10.1007/s12262-013-0965-6 -
Archivos Espanoles de Urologia Oct 2022To determine the predictive role of the neutrophil/lymphocyte ratio (NLR) in the prognosis and survival of patients with squamous cell carcinoma of the penis.
INTRODUCTION
To determine the predictive role of the neutrophil/lymphocyte ratio (NLR) in the prognosis and survival of patients with squamous cell carcinoma of the penis.
MATERIALS AND METHODS
A retrospective cohort study of 96 patients with squamous cell carcinoma of the penis (SCCP). Clinical and histological data, bloodwork and disease evolution information were collected. We determined neutrophil/lymphocyte ratios and analyzed their relationship to prognosis and survival.
RESULTS
The mean age of patients was 72,1 years. The average follow-up time for the sample was 3,8 years (CI 95%: 3,0-4,6). Compared to patients with NLR <3, those with NLR >3 presented a higher proportion of cancers in stages cN1 (29.7% vs 6.8%; = 0,004), stages pT3 and pT4 (24,3% vs 9,5%; = 0,05), and stages TNM III and IV (32,4% vs 10,2%; = 0,01); additionally, there were more cases of perineural invasion in the NLR >3 patients (29,7% vs 10,2%; = 0,03). The mean overall survival (OS) was 7,9 years (CI 95%: 6,2-9,6) and the cancer-specific survival (CSS), 1,3 years (CI 95%: 0,7-1,9). There were no differences in OS, CSS or in progression-free survival (PFS) in patients with NLR >3 compared to those with NLR <3 . However, in the Cox regression analysis, a higher NLR was independently associated (along with metastasis and need for adjuvant treatment) with lower PFS, with an HR: 1,27 (CI 95%: 1,02-1,57; = 0,02).
CONCLUSIONS
The utilization of NLR in clinical practice can be considered an additional tool to aid in the diagnosis and prognosis of patients with squamous cell carcinoma of the penis.
Topics: Male; Humans; Neutrophils; Prognosis; Retrospective Studies; Lymphocytes; Carcinoma, Squamous Cell; Penile Neoplasms; Penis
PubMed: 36330572
DOI: 10.56434/j.arch.esp.urol.20227508.102 -
Cancer Sep 2004Penile carcinoma is uncommon. Therefore, obtaining meaningful epidemiologic data requires analysis of large, multisource databases. The authors examined the association...
BACKGROUND
Penile carcinoma is uncommon. Therefore, obtaining meaningful epidemiologic data requires analysis of large, multisource databases. The authors examined the association between different demographic variables and the prevalence, presentation, and survival of patients with penile squamous cell carcinoma in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.
METHODS
The SEER database represents 12% of the U.S. population. The database included 1605 patients with a diagnosis of penile squamous cell carcinoma between 1973 and 1998. The variables analyzed were age, race, marital status, stage at presentation, type of surgery, performance of lymphadenectomy, and disease-specific survival.
RESULTS
Of 1605 patients, 37% presented with carcinoma in situ (CIS), 39% with localized disease, 13% with regional disease, 2.3% with distant disease, and 7.9% of the patients were unstaged. The percentage of patients presenting with CIS and localized disease increased and decreased yearly, respectively. African Americans represented 9.9% of the population and tended to present at a younger age and with a higher stage of disease, and their cancer-specific survival was shorter in all stages. However, these associations were statistically significant only for men with regional disease. Marital status was documented for 1394 patients (87%). The majority (84%) had a history of marriage and presented at an earlier stage of disease and had higher disease-specific survival in the localized (P = 0.0002) and regional stages (P = 0.0010) of disease.
CONCLUSIONS
The diagnosis of penile carcinoma significantly reduced survival. African-American men presented with a higher stage of disease and statistically significant decreased survival, whereas previously or currently married men presented at an earlier stage of disease and sought more aggressive treatment.
Topics: Adult; Black or African American; Age Factors; Aged; Carcinoma, Squamous Cell; Disease-Free Survival; Humans; Lymphatic Metastasis; Male; Marriage; Middle Aged; Neoplasm Recurrence, Local; Penile Neoplasms; Prognosis; Survival Analysis; United States
PubMed: 15316902
DOI: 10.1002/cncr.20519 -
European Journal of Surgical Oncology :... Jan 2019Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well... (Review)
Review
Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines-are provided. Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating. Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these tumours, dramatically on GCT and significantly on PeSCC. RARECAREnet data may permit to analyse how survivals may vary according to geographical areas, histology and age, leading to assume that non-homogeneous health-care resources may impact the cure and definitive outcomes. In support of this hypothesis, some epidemiologic datasets and clinical findings would indicate that survival may improve when appropriate treatments are delivered, linked to a different accessibility to the best health institutions, as a consequence of geographical, cultural and economic barriers. Finally, strong clues based on epidemiological and clinical data support the hypothesis that treatment delivered at reference centres or under the aegis of a qualified multi-institutional network is associated with a better prognosis of patients with these malignancies. The ERN EURACAN represents the best current European effort to answer this clinical need.
Topics: Cancer Care Facilities; Carcinoma, Squamous Cell; Delivery of Health Care; Europe; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Penile Neoplasms; Rare Diseases; Referral and Consultation; Survival Rate; Testicular Neoplasms
PubMed: 29526370
DOI: 10.1016/j.ejso.2018.02.006 -
Modern Pathology : An Official Journal... Feb 2021In the urinary tract, there is an uncertain relationship between intestinal metaplasia (IM), primary adenocarcinoma, and urothelial carcinoma. Although IM is usually...
In the urinary tract, there is an uncertain relationship between intestinal metaplasia (IM), primary adenocarcinoma, and urothelial carcinoma. Although IM is usually found adjacent to concurrent urothelial carcinoma or adenocarcinoma, small retrospective series have shown that most bladder biopsies with only IM do not subsequently develop cancer. However, IM with dysplasia does seem to be associated with a higher risk of concurrent malignancy or progressing to cancer. Since the molecular landscape of these lesions has remained largely unexplored, there are significant uncertainties about the oncogenic potential of IM in the bladder and urethra. This study investigated the presence of potentially oncogenic genetic variants in cases of IM with and without dysplasia. Twenty-three (23) cases of IM (3 urethra, 20 bladder) were sequenced using a solid tumor next-generation sequencing panel. Of these, five contained IM with high-grade dysplasia (including a case with paired IM-adenocarcinoma and another with paired IM-urothelial carcinoma) and 18 lacked dysplasia. Oncogenic genetic variants were found in all cases of IM with high-grade dysplasia and in five non-dysplastic IM cases, including mutations and copy number variants commonly seen in primary adenocarcinoma of the bladder and urothelial carcinoma. This study demonstrates that IM can harbor potentially oncogenic genetic variants, suggesting that it might represent a cancer precursor or a marker of increased cancer risk in a subset of cases.
Topics: Aged; Female; Humans; Intestines; Male; Metaplasia; Middle Aged; Oncogenes; Precancerous Conditions; Retrospective Studies; Urethra; Urinary Bladder
PubMed: 32860003
DOI: 10.1038/s41379-020-00655-z -
Pathobiology : Journal of... 2019Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1...
OBJECTIVE
Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1 blockade). Meanwhile, the FDA approved PD-1/PD-L1 inhibition treatment for any solid tumor showing MSI and/or defects in the MMR system. For squamous cell carcinoma (SCC) of the penis, no data on the frequency of MSI and altered MMR protein expression are available to date. Therefore, we investigated the MSI status and the expression of MMR proteins in a large cohort of penile SCCs.
METHODS
The MSI status of 105 archival formalin-fixed, paraffin-embedded penile SCCs was analyzed using the 5 markers of the NCI consensus panel for MIS testing (BAT25, 26, D2S123, D17S250, and D5S346), or, in cases without representative nontumorous tissue using a validated panel of 5 quasimonomorphic mononucleotide repeat markers (BAT 25, 26 and NR21, 24, 27). The expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 was analyzed using immunohistochemistry and a tissue microarray of a subset of penile SCCs from our cohort (n = 75).
RESULTS
Overall, in 96/105 cases, at least 4 microsatellite markers gave interpretable results. None of the cases showed MSI. Immunohistochemistry for MMR proteins was analyzable in 70/75 cases. All cases showed a regular expression of the MMR proteins.
CONCLUSION
MSI and defects in MMR protein expression are not regular features of penile SCC and might not act as biomarkers for PD-1/PD-L1 blockade therapy in penile carcinoma.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cohort Studies; DNA Mismatch Repair; Humans; Immunohistochemistry; Male; Microsatellite Instability; Microsatellite Repeats; Middle Aged; Paraffin Embedding; Penile Neoplasms
PubMed: 30650417
DOI: 10.1159/000495251 -
TheScientificWorldJournal Feb 2006Transitional cell carcinoma (TCC) is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU). The exact incidence of superficial... (Review)
Review
Transitional cell carcinoma (TCC) is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU). The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12-40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS) in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG) seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.
Topics: BCG Vaccine; Biopsy; Carcinoma, Transitional Cell; Disease Progression; Humans; Male; Mucous Membrane; Prostate; Prostatic Neoplasms; Recurrence; Risk Factors; Urethra; Urinary Bladder Neoplasms; Urothelium
PubMed: 17619737
DOI: 10.1100/tsw.2006.402