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Human Genomics Dec 2023The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.
BACKGROUND
The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.
METHOD
Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer.
RESULTS
Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer.
CONCLUSION
Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.
Topics: Carcinoma, Squamous Cell; Penile Neoplasms; Immunotherapy; Osteopontin; Biomarkers, Tumor; Gene Expression Profiling; Survival Analysis; Sequence Analysis, RNA
PubMed: 38111044
DOI: 10.1186/s40246-023-00558-5 -
The American Journal of Surgical... Dec 2023Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We...
Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte proliferation with variously elongated epithelial rete with premature squamatiziation, but regular superficial cornification, termed differentiated penile intraepithelial neoplasia (d-PeIN), were identified adjacent to 42/70 (60%) SCC (36/42 keratinizing ( P <0.001); 3 papillary, and 1 each verrucous, clear cell, sarcomatoid SCC). d-PeIN were associated with chronic inflammatory dermatoses (32/42; P <0.001), p53 overexpression (26/42; P <0.001), and hotspot mutations in TP53 (32/42; P <0.001), CDKN2A (26/42; P <0.001) or both (21/42; P =0.003) in the adjacent SCC. Cytoplasmic p16 ink4a overexpression in 5/42 d-PeIN correlated with CDKN2A missense mutations in the adjacent SCC. In all, 21/70 (30%) cornified verrucous or glycogenated verruciform precursors with minimal atypia and wild-type p53 (18/21; P <0.001) occurred adjacent to verrucous or papillary SCC (17/21; P <0.001) and keratinizing (4/21) SCC, which harbored mutations in HRAS and/or PIK3CA (12/21; P <0.004). Undifferentiated p16 ink4a -negative full-thickness precursors were identified in 7/70 (10%) SCC. Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS .
Topics: Male; Female; Humans; Papillomavirus Infections; Tumor Suppressor Protein p53; Human Papillomavirus Viruses; Skin Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Penile Neoplasms; Penis; Papillomaviridae; Class I Phosphatidylinositol 3-Kinases; Vulvar Neoplasms
PubMed: 37768009
DOI: 10.1097/PAS.0000000000002130 -
Nihon Hinyokika Gakkai Zasshi. the... Jan 1992It had been believed that carcinoma of the penis was rather rare in the developed countries comparing with that in the under-developing countries, however, the recent... (Review)
Review
It had been believed that carcinoma of the penis was rather rare in the developed countries comparing with that in the under-developing countries, however, the recent epidemiological studies failed to reveal any clear difference of the incidence of carcinoma of the penis all over the world. In these days so called successful treatment is coming to be evaluated by the quality of life (QOL) after surgical or nonsurgical treatment (especially sexual function tended to be considered very important factors altering QOL). I want to emphasize the following issues in this report. 1. Erythroplasia of Queyrat and Bowen's disease are carcinoma in situ and should be dealt as carcinoma of the penis. 2. relation of human papilloma virus and carcinoma of penis. 3. usefulness of TNM classification over Jackson's classification. 4. SCC antigen is a reliable tumor marker of carcinoma of the penis? 5. effectiveness of chemotherapy based on BLM combined with radiation therapy for carcinoma of the penis. 6. usefulness of Mohs microscopically controlled surgery and modified groin dissection. It is generally accepted that since carcinoma of the penis is a rare disease and for one institution up to 50 cases can be experienced during 20 years in Japan, there exist no integrated study involving a large number of institutions. I really wish a certain form of group study to be completed and the results from this study utilized to overcome the present problems for the treatment of carcinoma of the penis.
Topics: Antibiotics, Antineoplastic; Bleomycin; Combined Modality Therapy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Penile Neoplasms; Penile Prosthesis; Peplomycin; Prognosis; Quality of Life; Radiotherapy
PubMed: 1373451
DOI: 10.5980/jpnjurol1989.83.1 -
Annals of the Royal College of Surgeons... Jan 2010The Improving Outcomes Guidance (IOG) for patients with carcinoma of the penis states that treatment should be provided supraregionally to populations of 4 million or... (Comparative Study)
Comparative Study
INTRODUCTION
The Improving Outcomes Guidance (IOG) for patients with carcinoma of the penis states that treatment should be provided supraregionally to populations of 4 million or greater who treat over 25 cases of penis cancer each year. This study assesses the impact of this guidance on the management and outcomes of patients with the disease in our region.
PATIENTS AND METHODS
We retrospectively compared the records of 44 patients with carcinoma of the penis treated in our institution between 1969 and 1990 with 101 patients treated between 2002 and 2006, i.e. after supraregional centralisation of the service.
RESULTS
There was no significant change in the stage or grade of the tumours. However, the results show that, in modern times, there was a significant increase in the amount of penis-preserving and nodal surgery as well as a fall in mortality. The improved survival is greatest in patients with poorly-differentiated disease who may, therefore, have benefited from aggressive nodal surgery.
CONCLUSIONS
The centralisation of surgery for carcinoma of the penis results in improved outcomes both in terms of penis preservation and improved survival and this supports the IOG guidance.
Topics: Aged; Carcinoma; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Penile Neoplasms; Penis; Practice Guidelines as Topic; Retrospective Studies; Treatment Outcome
PubMed: 20056060
DOI: 10.1308/003588410X12518836439047 -
Advances in Anatomic Pathology May 2023Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis,... (Review)
Review
Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis, and testicles. Each tumor entity presents with unique biological characteristics, especially in terms of immunobiology. The immune landscape of genitourinary malignancies differs between immunoreactive tumors like urothelial carcinoma or carcinomas of the kidney, for which several immunotherapeutic treatment options have been approved in the past years. In contrast, prostate cancer presents with low immunogenicity and previous trials exploring immune checkpoint inhibitors and other immunotherapeutic agents did not proof substantial survival benefits. In this review, we are presenting a streamlined overview on the role of surgical pathologists within the contemporary practice of immune oncology. It includes current indications for pathologic programmed death-ligand 1 (PD-L1) assessment and important pathologic considerations on PD-L1 testing harmonization including interassay and algorithm variabilities. In addition, we will discuss emerging biomarkers beyond PD-L1 and their potential to predict immunotherapy responses including tumor mutational burden, microsatellite instability, gene expression signatures, and histologic factors.
Topics: Male; Humans; Urinary Bladder Neoplasms; B7-H1 Antigen; Carcinoma, Transitional Cell; Pathologists; Programmed Cell Death 1 Receptor; Biomarkers, Tumor; Immunotherapy
PubMed: 36730368
DOI: 10.1097/PAP.0000000000000383 -
Virchows Archiv : An International... Dec 2023The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of... (Review)
Review
The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of the accessory glands are the most relevant tumors, both from the morphologic and clinical point of view. An accurate diagnosis, grading and staging are essential for determining adequate treatment strategies and outcome. Information on anatomy and histology of the urethra is of fundamental importance in understanding the morphology of the tumors, including the clinical importance of their location and origin.
Topics: Humans; Male; Female; Urethra; Adenocarcinoma; Biomarkers, Tumor; Urethral Neoplasms
PubMed: 37233807
DOI: 10.1007/s00428-023-03565-y -
European Urology Focus Sep 2019Primary urethral cancer (PUC) is a rare cancer entity. Owing to the low incidence of this malignancy, the main body of literature consists mainly of case reports, making...
CONTEXT
Primary urethral cancer (PUC) is a rare cancer entity. Owing to the low incidence of this malignancy, the main body of literature consists mainly of case reports, making evidence-based management recommendations difficult.
OBJECTIVE
To review reported disease management strategies of PUC and their impact on oncological outcomes.
EVIDENCE ACQUISITION
A systematic research was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement using Medline, Scopus, and Web of Science, to find studies of the past 10yr including ≥20 patients, and investigating treatment strategies and their impact on outcomes of the three most frequent histologies: urothelial carcinoma, adenocarcinoma, and squamous cell carcinoma.
EVIDENCE SYNTHESIS
In localized PUC, penis-sparing surgery can be performed in males, while in females, complete urethrectomy with surrounding tissue is advised to minimize recurrence due to positive margins. Radiotherapy (RT) has worse survival and recurrence rates, as well as more adverse effects, than surgery, limiting its use in genital-preserving therapy. Locally advanced PUC should be treated with multimodal therapy, as monotherapies result in inferior recurrence and survival rates. Extent of surgery is still undecided, favoring radical cyst(oprostat)ectomy with total urethrectomy (RCU). Lymph node involvement is a predictor of survival, highlighting the role of lymph node dissection for disease control and staging. RT can improve survival in combination with surgery and/or chemotherapy (CHT). Neoadjuvant platinum-based CHT can improve overall and recurrence-free survival. At recurrence, salvage therapy with surgery and/or CHT can improve survival. Superficial urothelial carcinoma of the prostatic urethra can be treated with transurethral resection. Stromal invasion often features concomitant bladder cancer with a poor prognosis and requires RCU with or without systemic preoperative CHT.
CONCLUSIONS
PUC is a rare malignancy with an often poor natural course, requiring a stage- and gender-specific risk-based treatment strategy. The role of systematic perioperative CHT and the extent of surgery are becoming more important.
PATIENT SUMMARY
In this review, we looked at the treatment options for primary urethral cancer. We found that while an organ-confined disease can be managed with local resection, growth beyond the organ border makes a combination of different treatment modalities, such as surgery and systematic chemotherapy, necessary to improve outcomes.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Decision Trees; Female; Humans; Male; Urethral Neoplasms
PubMed: 31307949
DOI: 10.1016/j.euf.2019.07.001 -
Indian Journal of Surgical Oncology Mar 2017Sarcomatoid carcinomas are biphasic tumours, which occur at any site in the human body. It rarely affects the penis, with only 38 cases being reported in literature. It...
Sarcomatoid carcinomas are biphasic tumours, which occur at any site in the human body. It rarely affects the penis, with only 38 cases being reported in literature. It may be considered as a variant of squamous cell carcinoma or a dedifferentiated tumour. We report a 60-year old gentleman who presented with a swelling in the glans penis. He underwent a partial penectomy. Histopathology revealed sarcomatoid carcinoma of the penis, which was confirmed by immunohistochemistry. The rarity of this clinical entity makes its diagnosis difficult.
PubMed: 28127189
DOI: 10.1007/s13193-016-0531-3 -
Case Reports in Pathology 2017Penile carcinoma frequency varies widely in different parts of the world and comprises 1-10% of all the malignancies in males. Majority of the cases of penile carcinoma...
Penile carcinoma frequency varies widely in different parts of the world and comprises 1-10% of all the malignancies in males. Majority of the cases of penile carcinoma are squamous cell carcinoma of penis comprising 60% to 70% of all cases. Warty carcinoma of penis is an unusual neoplasm and a variant of penile squamous cell carcinoma comprising 5%-10% of all the variants. The other histological variants include basaloid, verrucous, papillary, sarcomatous, mixed, and adenosquamous carcinoma. The various histological entities with an exophytic papillary lesions including warty carcinoma are together referred to as the "verruciform" group of neoplasms. The warty carcinoma has to be differentiated from these lesions and is typically distinguished by histological features of hyperkeratosis, arborescent papillomatosis, acanthosis, and prominent koilocytosis with nuclear pleomorphism. We present a case of 65-year-old male with growth measuring 6 × 4 cm in the penis who underwent total penectomy and was diagnosed as warty carcinoma penis.
PubMed: 28154768
DOI: 10.1155/2017/2937592 -
PloS One 2022p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer...
p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer types is controversial. 15,783 samples from 124 different tumor types and 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. p16 was detectable in 5,292 (45.0%) of 11,759 interpretable tumors. Except from adenohypophysis in islets of Langerhans, p16 staining was largely absent in normal tissues. In cancer, highest positivity rates were observed in uterine cervix squamous cell carcinomas (94.4%), non-invasive papillary urothelial carcinoma, pTaG2 (100%), Merkel cell carcinoma (97.7%), and small cell carcinomas of various sites of origin (54.5%-100%). All 124 tumor categories showed at least occasional p16 immunostaining. Comparison with clinico-pathological data in 128 vulvar, 149 endometrial, 295 serous ovarian, 396 pancreatic, 1365 colorectal, 284 gastric, and 1245 urinary bladder cancers, 910 breast carcinomas, 620 clear cell renal cell carcinomas, and 414 testicular germ cell tumors revealed only few statistically significant associations. Comparison of human papilloma virus (HPV) status and p16 in 497 squamous cell carcinomas of different organs revealed HPV in 80.4% of p16 positive and in 20.6% of p16 negative cancers (p<0.0001). It is concluded, that a positive and especially strong p16 immunostaining is a feature for malignancy which may be diagnostically useful in lipomatous, urothelial and possibly other tumors. The imperfect association between p16 immunostaining and HPV infection with high variability between different sites of origin challenges the use of p16 immunohistochemistry as a surrogate for HPV positivity, except in tumors of cervix uteri and the penis.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Humans; Papillomaviridae; Papillomavirus Infections; Prevalence; Staining and Labeling; Urinary Bladder Neoplasms
PubMed: 35862385
DOI: 10.1371/journal.pone.0262877