Objective: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain in penile cancer has prognostic value and association with histopathological parameters, human papillomavirus (HPV), and clinical outcome.
Methods: PIK3CA copy number status was assessed with fluorescence in situ hybridization in tissue microarrays generated from archival paraffin embedded blocks of 199 patients with primary penile squamous cell carcinoma (PSCC). HPV DNA was detected with INNO-LiPA assay.
Background: Therapeutic targeting of the PI3K-AKT-mTOR pathway may benefit patients with advanced penile squamous cell carcinoma (PSCC).
Objectives: To determine the prevalence of PIK3CA copy number gain and correlate this with the activity status of PI3K-AKT-mTOR pathway in pre-malignant penile intraepithelial neoplasia (PeIN) and invasive PSCC.
Materials And Methods: Archival tissue blocks were obtained from 58 PeIN and 244 primary PSCC patients treated at St George's Hospital.
Objectives: To determine whether phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha (PIK3CA) copy number gain is common and could prove a useful marker for the activation status of the PI3K-AKT-mTOR pathway in penile squamous cell carcinoma (PSCC).
Methods: Fresh frozen tissue and archival blocks were collected from 24 PSCC patients with 15 matched normal penile epithelium (NPE) tissue from St George's Hospital. PIK3CA mutational and copy number status (CNS) was assessed via Sanger sequencing and fluorescence hybridisation, respectively.
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations.
View Article and Find Full Text PDFThe International Society of Urological Pathology (ISUP) held an expert-driven penile cancer conference in Boston in March 2015, which focused on the new World Health Organisation (WHO) classification of penile cancer: human papillomavirus (HPV)-related tumours and histological grading. The conference was preceded by an online survey of the ISUP members, and the results were used to initiate discussions. Because of the rarity of penile tumours, this was not a consensus but an expert-driven conference aimed at assisting pathologists who do not see these tumours on a regular basis.
View Article and Find Full Text PDFPenile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status.
View Article and Find Full Text PDFGenome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis.
View Article and Find Full Text PDFBasal cell carcinoma of the prostate (BCP) is a neoplasm composed of prostatic basal cells. There are only a few publications outlining the diagnosis, treatment, prognosis and outcome for BCP. Traditionally surgery has been used but these tumors also respond to concomitant chemo-radiotherapy.
View Article and Find Full Text PDFBackground: Dynamic sentinel node biopsy (DSNB) in combination with ultrasound scan (USS) has been the technique of choice at our centre since 2004 for the assessment of nonpalpable inguinal lymph nodes (cN0) in patients with squamous cell carcinoma of the penis (SCCp). Sensitivity and false-negative rates may vary depending on whether results are reported per patient or per node basin, and with or without USS.
Objective: To determine the long-term outcome of patients undergoing DSNB and USS-guided fine-needle aspiration cytology (FNAC) in our cohort of newly diagnosed cN0 SCCp patients, as well as to analyse any variation in sensitivity of the procedure.
Aims: To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival.
Methods: 148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein.
Background: The European Association of Urology (EAU) guidelines advise an elective bilateral lymphadenectomy in clinically node-negative (cN0) patients with high-risk penile carcinoma (≥pT2, G3, or lymphovascular invasion [LVI]).
Objective: Our aim was to assess prognostic factors for occult metastasis and to determine whether current EAU guidelines accurately stratify patients at high risk.
Design, Setting, And Participants: Data of 342 cN0 patients with histologically proven invasive penile squamous cell carcinoma who had undergone the current dynamic sentinel node biopsy (DSNB) protocol were analysed.
Objective: To report on the largest series to date of ulceration of the external genitalia, related to treatment with nicorandil - a vasodilator for the prevention and long-term treatment of angina - and to review the literature on the subject, focusing on the clinical features and the pathogenesis of this rare, yet marked, side-effect.
Patients And Methods: Three patients (aged 71-83 years) were referred for severe ulceration of the penis. A complete work-up was performed to exclude potential underlying causes, including malignancy and sexually transmitted diseases.
Background: The risk of lymph node (LN) metastasis in G2T1 penile cancer has been previously reported as 0-50% and is classified as "intermediate" in the European Association of Urology (EAU) guidelines. The management of impalpable regional nodes in this cohort of patients remains contentious and varies among treatment centres depending on tumour factors and local resources.
Objectives: To establish the risk of LN metastasis in G2T1 disease.
Objective: To examine the presentation, management and outcomes of patients with renal angiomyolipoma (AML) over a period of 10 years, at St George's Hospital, London, UK.
Patients And Methods: We assessed retrospectively 102 patients (median follow-up 4 years) at our centre; 70 had tuberous sclerosis complex (TSC; median tumour size 3.5 cm) and the other 32 were sporadic (median tumour size 1.
Purpose: Sentinel node biopsy is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection. Reservations about the use of sentinel node biopsy include the fact that most current results come from one institution and the supposedly long learning curve associated with the procedure.
View Article and Find Full Text PDFObjective: To integrate the mapping of ERG alterations with the collection of expression microarray (EMA) data, as previous EMA analyses have failed to consider the genetic heterogeneity and complex patterns of ERG alteration frequently found in cancerous prostates.
Materials And Methods: We determined genome-wide expression levels with GeneChip Human Exon 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 35 specimens of prostate cancer from 28 prostates.
Objective: To reinvestigate whether South Asian men in the UK are at lower risk of being diagnosed with prostate cancer in a UK-based retrospective cohort study and to examine possible reasons that may explain this.
Patients And Methods: The catchment areas were predefined in four areas of southern England, and age- and race-specific populations for those areas taken from census data. Cases were ascertained through review of multiple hospital sources, while race, other demographic factors, and medical history were determined using questionnaires sent to the men, hospital records review and death certificates.
Objective: To examine the tissue expression of DNA topoisomerase I (Topo I) and IIalpha (Topo II), to pursue the possibility of future chemotherapy regimens for squamous cell carcinoma of the penis (SCCP), as high expression of Topo I might indicate sensitivity to the camptothecins, whereas high Topo II might indicate sensitivity to etoposide.
Patients And Methods: In all, 73 patients with SCCP were reviewed and then tissue samples microarrayed. These were then stained with immunohistochemistry for Topo I, Topo II and Ki-67.
Translocation of TMPRSS2 to the ERG gene, found in a high proportion of human prostate cancer, results in overexpression of the 3'-ERG sequences joined to the 5'-TMPRSS2 promoter. The studies presented here were designed to test the ability of expression analysis on GeneChip Human Exon 1.0 ST arrays to detect 5'-TMPRSS2-ERG-3' hybrid transcripts encoded by this translocation.
View Article and Find Full Text PDFObjective: To evaluate the introduction of dynamic lymphoscintigraphy and sentinel lymph-node (SLN) biopsy (used to detect occult lymph node metastases in patients with penile cancer and clinically impalpable inguinal lymph nodes at presentation) at a UK tertiary referral centre for penile cancer.
Patients And Methods: In all, 75 patients with penile squamous cell carcinoma of stage T1, grade > or = 2, and unilateral or bilateral impalpable groin nodes, were prospectively enrolled over a 2-year period. Patients underwent lymphoscintigraphy with (99m)technetium-labelled nanocolloid which was injected intradermally around the tumour or into the distal penile shaft skin.
Objectives: It is known that African American men have a greater risk of prostate cancer than white men. We investigated whether this was true for first-generation black Caribbean and black African men in the United Kingdom.
Methods: A clinical cohort study design recruiting all cases of prostate cancer diagnosed over a 5-yr period and residing in defined areas of London and Bristol.
Objective: To report our initial experience of total glans resurfacing (TGR), as premalignant lesions of the glans penis have conventionally been treated by local excision, topical chemotherapy, laser or cryotherapy, but these techniques are frequently associated with high local failure rates and unsightly scarring that can make monitoring by gross inspection difficult.
Patients And Methods: TGR involves removing the glans and subcoronal epithelial and subepithelial tissues down to the corpus spongiosum of the glans and Buck's fascia at the coronal sulcus. The denuded glans penis is then covered with an extra-genital skin graft.
Objective: To determine the incidence of balanitis xerotica obliterans (BXO) in a consecutive series of penile carcinomas in one centre, as BXO is a common penile disease that usually involves the prepuce and glans, and there have been sporadic case reports of the association between BXO and penile carcinoma, although it is uncertain if there is a specific causal relationship.
Patients And Methods: The reported incidence of penile carcinoma in patients with BXO is 2.6-5.
Objective: To determine the presence or absence of micrometastases in lymph node dissection specimens of men with squamous cell carcinoma (SCC) of the penis using immunohistochemistry, and to correlate the results with clinical outcome.
Patients And Methods: In all, 13 men (mean age 55.8 years) with penile SCC, treated at St George's hospital between 2001 and 2005, were selected.