Extra-target low-risk prostate cancer: implications for focal high-intensity focused ultrasound of clinically significant prostate cancer.

PURPOSE: To analyse the impact of the presence of extra-target non-clinically significant cancer (NCSC) after high-intensity focused ultrasound (HIFU) hemiablation on oncological results. To analyse radical treatment free survival (RTFS) rates at 2-3 years follow-up. METHODS: Retrospective single-centre study of 55 patients treated by primary HIFU hemiablation from 2010 to 2016. Inclusion criteria were unilateral MRI detected CSC, stage ≤ T2b, Gleason score (GS) ≤ 7, at least 6 mm distant from prostate apex. MRI with systematic and targeted biopsies was performed at diagnosis. Follow-up included clinical examination, PSA every 6 month, MRI and biopsies at 1 year and in case of PSA elevation. HIFU retreatment was possible. Whole-gland treatment was indicated in case of positive biopsies with GS ≥ 7 or maximum cancer core length > 5 mm, any GS. RESULTS: Mean follow-up was 33 months (SD: 17-49 months). Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS at univariate analysis (p = 0.29). 10 (18%) patients had a salvage whole-gland treatment after a median follow-up of 26 months (IQR 17-28). RTFS at 2 and 3 years were 92% and 80%. CONCLUSION: Presence or not of an extra-target NCSC in the untreated part of the gland had no impact on RTFS. NCSC lesion can be left untreated and actively monitored. RTFS was 80% at 3 years which support the concept of focal/partial treatment as a treatment option of CSC prostate cancer.

[Evolution of the number of incident cases, stage and first treatments for prostate cancer in France between 2001 and 2016]. / Évolution du nombre de cas incidents, du stade et des premiers traitements des cancers de la prostate en France entre 2001 et 2016. À partir de données hospitalières de 3 centres.

INTRODUCTION: No studies of French hospital registries for prostate cancer (PCa) have been published since the 2012 USPSTF recommendations. MATERIAL: This is a multicenter cohort study based on hospital data of prostate biopsies (PB) in 3 health centers between 2001 and 2016. The main objective is to describe the evolution of incident cases of PCa. The secondary objectives are to describe the number of cases per stage of PCa and the distribution of the first treatments. RESULTS: In total, 11,491 PB series diagnosed 5927 cases of PCa. The median age was 67 [61-73] years and the median PSA was 7.8 [5.5-13] ng/mL. The number of cases increased until 2006 before decreasing from 2006 to 2013 and then stabilizing from 2013 to 2016. The proportion of incident cases was: (1) for the stable metastatic stage around 8 [7-10]%, (2) for cases with PSA<10 ng/mL increasing from 46% to 75% in 2010 down to 64% in 2016, (3) for the grade 1 group decreasing from 59% to 33 % between 2011 and 2016. The proportion of active surveillance treatment for low-risk cancers increased from 5 to 60% and surgery decreased from 73 to 33%. CONCLUSION: The evolution of the incident cases showed a decrease from 2006 to 2013 and a stability until 2016. The number of cases with PSA<10 ng/mL decreased since 2010 and the proportion of the options of treatment by surveillance increased strongly to the detriment of the surgery for low risks. LEVEL OF EVIDENCE: 3.

Comprehensive molecular classification of localized prostate adenocarcinoma reveals a tumour subtype predictive of non-aggressive disease.

Background: Management of localized prostate cancer (PCa) is a major clinical challenge since most of these cancers would not evolve but a majority of patients will still undergo a life-changing radical surgery. Molecular studies have shown that PCa can be classified according to their genomic alterations but none of the published PCa molecular classifications could identify a subtype corresponding to non-evolutive tumours. Materials and methods: Multi-omics molecular profiling was carried out on post-radical prostatectomy material from a cohort of 130 patients with localized PCa. We used unsupervised classification techniques to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression. Merged data from our cohort and The Cancer Genome Atlas cohort were used to characterize the resulting tumour subtypes. We measured subtype-associated risks of biochemical relapse using Cox regression models and survival data from five cohorts including the two aforementioned. Results: We describe three PCa molecular subtypes associated with specific molecular characteristics and different clinical outcomes. Particularly, one subtype was strongly associated with the absence of biochemical recurrence. We validated this finding on 746 samples from 5 distinct cohorts (P = 3.41 × 10-8, N = 746 tumour samples), and showed that our subtyping approach outperformed the most popular prognostic molecular signatures to accurately identify a subset of patients with a non-evolutive disease. We provide a set of 36 transcriptomic biomarkers to robustly identify this subtype of non-evolutive cases whose prevalence was estimated to 22% of all localized PCa tumours. Conclusion: At least 20% of patients with localized PCa can be accurately predicted to have a non-evolutive disease on the basis of their molecular subtype. Those patients should not undergo immediate surgery and rather be placed under active surveillance.

[Pathology findings after radical prostatectomy for prostate cancer in patients eligible for active surveillance: Contribution of multiparametric MRI to treatment decision]. / Résultats anatomopathologiques après prostatectomie totale pour cancer chez des patients éligibles à une surveillance active : apport de l'IRM multiparamétrique dans la décision de traitement.

OBJECTIVES: To analyze, in patients with prostate cancer (PC) potentially eligible for active surveillance (AS), whether multiparametric-MRI (mp-MRI) predicts presence of clinically significant cancer on radical prostatectomy (RP) specimen. METHODS: We identified 77 men with PC eligible for AS (PSA≤15ng/mL, stage≤T2a, Gleason score≤6, up to 3 positive cores, maximal cancer core length≤5mm) who underwent RP between 01/2008 and 08/2015. All patients had prebiopsy mp-MRI followed by systematic±targeted biopsies. For each patient, the likelihood of the presence of cancer on mp-MRI was assigned using Likert scale (1 to 5). The predictive factors for the presence of significant cancer on RP specimen (Gleason score≥7 and/or tumoral maximal diameter>10mm) were evaluated using logistic regression. RESULTS: Median age was 61 and median PSA was 6.7ng/mL. Overall, 49 (64%) patients had a positive mp-MRI (score≥3). Clinically significant cancer on RP specimen was found in 45 (58%) patients (69% in MRI-positive patients vs 39% in MRI-negative patients). In multivariate analysis, a positive MRI was a predictive factor for the presence of significant cancer on the surgical specimen (OR=3.0; CI95% [1.01-8.88]; P=0.04), as was age (OR=1.17; CI95% [1.05-1.31]; P=0.004) and PSAD (OR=1.10; CI95% [1.01-1.20]; P=0.02). CONCLUSION: Mp-MRI is a useful exam for selecting patients eligible for AS even if the situation remains unclear after prostate biopsies including targeted biopsies. Upon confirmation by further studies, mp-MRI should be considered as an independent criterion before entering an AS program. LEVEL OF EVIDENCE: 4.

SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1-mutated patient's management.

Steroidogenic factor 1 (encoded by SF1/NR5A1) is a transcription factor with multiple target genes involved in the development and function of multiple steroidogenic and non-steroidogenic tissues. NR5A1 mutations lead to several phenotypes, including sex reversal, spermatogenesis failure, premature ovarian failure and adrenocortical insufficiency. The implication of NR5A1 mutations in spleen development anomalies was recently highlighted. We provide new evidence of this involvement, describing a novel heterozygous non-sense NR5A1 mutation in a 46,XY-DSD with polysplenia female proband and her father, who had hypospadias and asplenia.

[Long term biochemical recurrence free survival after radical prostatectomy for cancer: comparative analysis according to surgical approach and clinicopathological stage]. / Survie sans récidive biologique à long terme après prostatectomie totale pour cancer: analyse comparative selon la voie d'abord et le stade clinico-pathologique.

OBJECTIVE: To assess long term biochemical recurrence free survival after radical prostatectomy according to open, laparoscopic and robot-assisted surgical approach and clinicopathological stage. MATERIAL AND METHODS: A cohort study of 1313 consecutive patients treated by radical prostatectomy for localized or locally advanced prostate cancer between 2000 and 2013. Open surgery (63.7%), laparoscopy (10%) and robot-assisted laparoscopy (26.4%) were performed. Biochemical recurrence was defined by PSA>0,1ng/mL. The biochemical recurrence free survival was described by Kaplan Meier method and prognostic factors were analysed by multivariable Cox regression. RESULTS: Median follow-up was 57 months (IQR: 31-90). Ten years biochemical recurrence free survival was 88.5%, 71.6% and 53.5% respectively for low, intermediate and high-risk D'Amico groups. On multivariable analysis, the worse prognostic factor was Gleason score (P<0.001). Positive surgical margins rate was 53% in pT3 tumours and 24% in pT2 tumours (P<0.001). Biochemical recurrence free survival (P=0.06) and positive surgical margins rate (P=0.87) were not statistically different between the three surgical approaches. CONCLUSION: Biochemical recurrence free survival in our study does not differ according to surgical approach and is similar to published series. Ten years biochemical recurrence free survival for high-risk tumours without hormone therapy is 54% justifying the role of surgery in the therapeutic conversations in this group of tumours. LEVEL OF EVIDENCE: 3.

[Pathologic analysis of upper tract urothelial carcinomas: state of the art review for the yearly scientific report of the French National Association of Urology]. / Anatomopathologie des tumeurs de la voie excrétrice urinaire supérieure: état de l'art pour le rapport annuel de l'Association française d'urologie.

PURPOSE: Upper tract urothelial carcinomas (UTUC) are rare tumors. Pathologist have a crucial role in establishing the diagnosis and the evaluation of the prognosis of these tumors. MATERIAL AND METHODS: A systematic review of the scientific literature was performed in the Medline database (PubMed) using different associations of the following key words alone or concomittantly: ureter; renal pelvis; urothelial carcinoma; specimen; pathology; histology; classification; grade; stage; prognosis. A particular search was done on the characteristics of the specimen management provided by urologists to pathologists and main prognostic specificities expected in UTUCs. RESULTS: Urinary cytology and biopsies are useful to provide the grade of the tumor according to the WHO classification 2004. The urologist needs to depict the clinical context to the pathologist in order to eliminate differential diagnosis. The main prognostic informations provided by the pathologist from the specimen analysis are the following: stage (TNM 2009), grade (WHO 2004), carcinoma in situ, location within upper tract, multifocality, necrosis, tumor size, lymphovascular invasion, margins and potentially microsatellite status when a HNPCC case is suspected. CONCLUSION: The pathologic analysis of a UTUC specimen needs nowadays to fulfill standardised international criteria of quality. However, specific additional aspects reported in the literature (e.g., lymphovascular invasion) are not systematically depicted.

Significance of ADC value for detection and characterization of urothelial carcinoma of upper urinary tract using diffusion-weighted MRI.

PURPOSE: To evaluate utility of diffusion-weighted magnetic resonance imaging (DWI) to detect and predict the histological characteristics of upper urinary tract urothelial carcinomas (UTUCs). MATERIALS AND METHODS: We retrospectively evaluated 20 suspicious lesions from 19 patients. MRI study included conventional sequences and DWI with apparent diffusion coefficient (ADC) maps calculated between b = 0 and b = 1,000. ADC values were measured within two different regions of interest (ROI): a small identical ROI placed in the most restrictive part of the tumour and a larger ROI covering two-thirds of the mass surface. The mean ADC values of the tumours were compared with that of normal renal parenchyma using an unpaired Student's t test. Association between ADC values and histological features was tested using non-parametric tests. RESULTS: Overall, 18 tumours were confirmed histologically as UTUCs. DWI failed to detect two cases of UTUCs (one CIS and one small tumour of 5 mm). There was no statistically significant difference in ADC values measured with the small or large ROI (p = 0.134). The mean ADC value of UTUC was significantly lower than that of the normal renal parenchyma (p < 0.001). No statistical association was found between ADC values and pathological features (location, p = 0.35; grade, p = 0.98; muscle-invasive disease, p = 0.76 and locally advanced stage, p = 0.57). CONCLUSION: DWI may be interesting tool for detecting UTUCs regarding the difference of ADC values between the tumours and surrounding healthy tissues. In regard to low frequency of UTUCs, the association of ADC values and histological characteristics need further investigations in a large prospective multi-institutional study.

[Elements of completeness and results of the first year of registration of the "Registre général des cancers de Lille et de sa région"]. / Éléments d'exhaustivité et résultats pour la première année d'enregistrement du Registre général des cancers de Lille et de sa région.

BACKGROUND: In 2005, following the first cancer plan of the national health authorities, a general cancer registry was established in northern France, in a territory designated as a "zone in proximity to the city of Lille" (ZPL). The aim of the present work was to evaluate the completeness of the registry's first year of incident cancer registration (2005) and to compare the observed cancer incidence in the "ZPL" with the estimated incidence in France. METHODS: Completeness was assessed using the average number of sources per case, the percentage of histological verification and a method of independent case ascertainment (mortality/incidence ratio). A direct standardization on the world population was used to calculate the ZPL/France ratios of standardized incidence rates. Analyses were conducted for 21 cancer sites. RESULTS: In 2005, 3635 cases of invasive cancer were recorded by the registry. The average number of sources per case was 2.7 and histological proof was available for 91.4% of cases. Mortality/incidence ratios showed satisfactory completeness of the data for men for most cancer sites. For women however, for cancer sites for which the number of cases was low, data will have to be confirmed during the subsequent years of observation. A lack of completeness was found for cutaneous melanoma. In men, an overincidence was identified for cancers of lip-mouth-pharynx, larynx, esophagus, lung, liver, bladder, kidney and colon-rectum. In women, an overincidence has been identified for cancers of lip-mouth-pharynx, liver, bladder, colon-rectum, corpus uteri and ovaries. CONCLUSION: The first year of incidence validated at the "Registre général des cancers de Lille et de sa région" shows a completeness of records with regards to studied criteria. The comparison with national data shows an overincidence of cancers related to tobacco and alcohol consumption in the geographical area covered by the registry. The incidence of lip-mouth-pharynx cancer in men is the highest of all French registries.

[Small renal masses: 10 years of treatment in a tertiary referral center in cancer research]. / Cancer du rein de moins de 4cm : traitement dans un centre de référence régional en cancérologie.

OBJECTIVES: To analyze the impact of preoperative clinical data that could influence the undertaking of small renal masses (size<4cm) and to direct patients towards surgery or observance or radiofrequency. PATIENTS AND METHODS: From January 2000 to December 2010, 253 small renal masses were included in a retrospective study. Renal masses less than 3cm were compared to the 3 to 4cm masses. Clinical data, pathological data and follow-up was noted prospectively on the database and we analyzed it according to the treatment done (surgery, radiofrequency or observation). RESULTS: Surgical treatment, radiofrequency and observation were performed for 214 (86.4%), 15 (5.9%), and 24 (9.5%) patients respectively. The treatments of the patients differed in the two groups (<3cm vs. 3-4cm) and the appeal to radiofrequency and observation was more frequent for elder patients (>65years old) and for those whom performance status (ECOG status) greater or equal to 1. Cancer specific survival was not statistically different for the two groups (average: 87.5% after 5years, mean 33months follow-up, P=0.7). Independent risk factors of recurrence were Fuhrman grade, synchronous tumors, noddles invasion and metastatic progression. Positive surgical margins were not a risk factor of recurrence (P=0.6). CONCLUSION: Age and performance status are the two main clinical data, which influence the treatment for patients with small renal masses. Radiofrequency and observation were undertaken more regularly for elder and altered ones. The use of scales as Charlson Index or Lee scale could help to choose more easily according to global morbidity and mortality.

[Management of testicular lesions in a population of infertile patients]. / Prise en charge des nodules testiculaires dans une population de patients infertiles.

INTRODUCTION: Testicular parenchyma abnormalities and testis cancers are more frequent in infertile men, hence the guidelines recommending a systematic scrotal ultrasound. METHODS: A retrospective review of all patients treated with total or partial orchidectomy, from January, 2000 to July, 2010, for a testicular lesion discovered during an infertility evaluation work-up. Physical, examination data, type of surgery and pathological results were reported. RESULTS: Forty-five patients were treated. The majority of tumors (80%) were non palpable, and incidentally discovered with scrotal ultrasonography. Eight cases were partial orchidectomies, and 37 cases were radical orchidectomies. A frozen section examination was performed in 13 cases, and led to two radical orchidectomies. Standard histological examination revealed 33 (73.3%) benign lesions (11 Leydig cell hyperplasias, 17 Leydig cell tumors, five Sertoli cell tumors) and 10 (22.2%) malignant lesions (nine seminomas and one teratoma). Ten patients had a Klinefelter syndrome, for whom all the lesions were benign. CONCLUSION: The majority of non-palpable testicular lesions, discovered by ultrasonography in a population of infertile men were benign tumors. Conservative management in this context appears to be an option, to preserve the endocrine function and the fertility of these patients, while being ontologically safe.

[Renal cell carcinoma of patients younger than 40 years old]. / Le carcinome à cellules rénales du sujet de moins de 40ans.

CONTEXT: Clinical and pathological characteristics of renal cell carcinoma (RCC) of patients younger than 40 years old are not well known. The objective of this study was to analyze these characteristics by comparison to a group of patients aged 58 to 62. METHODS: Retrospective study of a group of patients aged less than 40 years old (group 1, n=44) and a group of patients aged 58 to 62 years old (group 2; n=106) treated surgically for a renal mass from January 2000 to July 2009. A comparative analysis of clinical, pathological characteristics and of cancer-specific survival was performed. Specific survival was calculated with the Kaplan-Meier method and compared with the Log-Rank test. Univariate and multivariable analysis were performed to assess and quantify the effect of age on cancer-specific survival. Covariates were gender, age group, tumor size, pT stage, histological sub-type and Fuhrman grade. RESULTS: Clinical and pathological characteristics were similar in both groups (P>0.05) except for histological sub-type (56% of clear cell RCC for group 1 versus 82% for group 2). In the group of patients younger than 40 years, translocation RCC represented 23% of all RCCs. Cancer-specific survival at five years was similar in both groups (80% and 76% for group 1 and 2 respectively, P>0.58). Fuhrman grade was the only independent prognostic factor of cancer-specific survival (P=0.001). CONCLUSION: Patients younger than 40 years were more likely to have a translocation RCC than their older counterparts for who clear cell RCC represented the main histological sub-type. Cancer-specific survival was similar between both groups. Only a systematic specific immunostaining for TFE3 or TFEB will allow to assess the exact incidence and prognosis of this entity.

[Renal extramedullary hematopoiesis]. / Hématopoïèse extramédullaire rénale.

Extramedullary hematopoiesis (EMH) refers to the location of hematopoietic elements in locations other than the bone marrow medullary space. EMH is an uncommonly isolated disease and it usually occurs during chronic hematologic disorders due to hematopoiesis hyperstimulation. Reticuloendothelial system is the most common site of EMH whereas the kidney is an extremely rare location. EMH lesions are frequently asymptomatic, nevertheless hemorrhagic manifestations can be observed. Patient history can help for making a diagnosis, which can be established by CT scan and/or MRI. Surveillance is recommended for asymptomatic cases while local therapies such as low dose radiation or surgery can be used to treat bleeding lesions. Systemic therapies using iron supplementation or blood transfusion are helpful to avoid disease recurrence. We report a case of pyelocaliceal EMH managed with laser vaporization during ureteroscopy procedures.

[Photodynamic therapy and prostate cancer]. / Thérapie photodynamique et cancer de la prostate.

PURPOSE: Photodynamic therapy (PDT) is an innovative therapeutic modality in urologic oncology. MATERIAL AND METHODS: We reviewed the current literature on principles and modalities of PDT in prostatic oncology. RESULTS: Focal therapy of prostate cancer is an application field of PDT. Clinical phase II studies are ongoing to determine PDT efficacy and safety in this indication. PDT as salvage treatment after prostatic radiotherapy has been tested. Carcinologic results were promising but important side effects were reported. Individual dosimetric planification is necessary to avoid this toxicity. CONCLUSION: PDT first clinical experience for prostate cancer has showed its technical feasibility. Several research ways are currently in study to improve carcinologic efficacy and to limit potential side effects.

[Oncologic outcomes after radical prostatectomy: French validation of the D'Amico risk group classification]. / Résultats carcinologiques après prostatectomie totale pour cancer: validation française de la classification de D'Amico.

PURPOSE: To validate the D'Amico risk group classification in French consecutive series and to analyse recurrence risk factor after radical prostatectomy (RP) for prostate cancer. MATERIAL: We retrospectively analyzed data collected from 10/2000 to 05/2009 for 730 consecutive patients who underwent RP for clinically localized or locally advanced prostate cancer (cT1-cT3) in our institution. Biochemical recurrence (BCR) was defined by prostate-specific antigen (PSA) of greater than 0.1 ng/ml, with rising PSA at two consecutive dosages. Postoperative survival was estimated using the Kaplan-Meier method after D'Amico's group stratification. The accuracy of the model was evaluated using the Harrell's concordance index. The impact on outcomes of preoperative PSA and pathological features was evaluated using a monovariate and multivariate Cox analysis. RESULTS: Median follow-up was 30 months [interquartile range: 13-51]. The overall 3-year and 5-year probability of freedom from BCR was 85% (95% Confidence Interval (CI), 81-88%) and 78% (95% CI, 74-83%), respectively. For low, intermediate, and high-risk group, the 5-year freedom from BCR was 92% (95% CI, 88-97%), 73% (95% CI, 65-81%) and 44% (95% CI, 28-59%), respectively (p<0.001). Harrell's concordance index was 0.71. Surgical margins were positive in 31% of all cases. In a multivariate analysis, preoperative PSA, pathological tumor stage, Gleason score and surgical margins status predicted BCR after RP. CONCLUSIONS: We externally validated the ability of the D'Amico's risk group stratification to predict disease progression following RP in European patients. Preoperative PSA, pathological stage, Gleason score and surgical margins status predicted BCR after RP in our series through a multivariate analysis.

[Prognostic significance of lymphovascular invasion in upper urinary tract carcinoma: a retrospective monocentric analysis]. / Rôle pronostique des emboles vasculaires tumoraux dans les tumeurs des voies excrétrices urinaires supérieures : analyse rétrospective monocentrique.

OBJECTIVE: To analyze the prognostic impact of lymphovascular invasion (LVI) in case of urothelial carcinoma of upper urinary tract (UUT-UC). PATIENTS AND METHODS: Retrospective study of 83 consecutive patients treated surgically for UUT-UC between January 1998 and October 2008. Prognostic interest of histopathological factors (stage, grade, LVI, CIS, tumor architecture, location, nodal status and surgical margins) was assessed in univariate and multivariate Cox regression model. Specific survival (SS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were calculated using Kaplan-Meier method and Log-Rank test. RESULTS: LVI was observed in 26.5% of patients after histopathologic reviewing. The SS, RFS and MFS at 2 years were 93%, 76% and 96% respectively in group without LVI compared to 40%, 13% and 38% in group with LVI (P<0.001). In univariate analysis, pathological stage, LVI and margin status were predictive of SS (P<0.05). Pathological stage, LVI and surgical margin status were predictive of RFS (P<0.05). LVI, tumor architecture and status of surgical margins were predictive of MFS (P<0.05). LVI was the only independent predictive factor in multivariate analysis for all survival (P=0.002, 0.002 and 0.001 respectively for the SS, RFS and MFS). CONCLUSION: LVI was a poor prognostic factor in cases of UUT-UC. This criteria should be routinely sought and included in the pathology report.

Radiological assessment of mandibular invasion in squamous cell carcinoma of the oral cavity and oropharynx.

BACKGROUND: Preoperative assessment of mandibular bone invasion in squamous cell carcinoma of the oral cavity and oropharynx is crucial for optimizing bone resection. The principal aim of this study was to evaluate the diagnostic value of CT and MR imaging for the diagnosis of mandibular bone invasion compared to the histological reference. In addition, we assessed the survival impact of bone invasion. PATIENTS AND METHODS: A single-center retrospective study included all consecutive patients treated by mandibular bone interruption for squamous cell carcinoma of the oral cavity and/or oropharynx. RESULTS: Sixty-eight patients were included. Prevalence of bone invasion on histology was 43%. Sensitivity, specificity and positive and negative predictive value were respectively 70%, 71%, 66% and 76% for CT compared with histologic analysis, 83%, 50%, 59% and 78% for MRI, and 83%, 62% 62%, 83% for associated CT and MRI. The two tests showed good agreement, with kappa index 0.69 (95% CI, 0.49-0.89) (P<0.0001). There was no difference in overall survival (log-rank>0.70) between the groups with and without bone invasion. CONCLUSION: CT and MRI are complementary for preoperative assessment of mandibular bone invasion, be it cortical and/or medullary, and in some cases may allow mandibular bone-sparing.

Increased expression and altered intracellular distribution of adhesion/growth-regulatory lectins galectins-1 and -7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas.

AIMS: To examine the level of expression of the pleiotropic regulators galectins-1 and -7 in relation to neoplastic progression of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas. METHODS AND RESULTS: The presence of galectins-1 and -7 was investigated using quantitative immunohistochemistry in (i) a series of 78 HSCCs by comparison with 17 normal epithelia (N_E), 26 low-grade dysplasia (low_D) and 27 high-grade dysplasia (high_D) and (ii) a series of 56 LSCCs by comparison with 50 N_E, 23 low_D and 29 high_D. Galectin-1 positivity expressed as a percentage of cells was significantly higher in carcinomas (HSCCs and LSCCs) than in N_E, low_D or high_D (P < 10(-6)). Galectin-7 expression was elevated in low_D (P = 0.0004) compared with N_E and in carcinomas (HSCC) compared with high_D (P = 0.0002). Tumour progression from high_D to carcinomas was associated with a shift of galectin-1 localization from the nucleus towards the cytoplasm. Increased expression of galectin-7 in dysplasias was accompanied by a shift from the cytoplasmic compartment (N_E) to the nucleus (low_D and high_D). CONCLUSIONS: Our data reveal an association between the level of presence of galectins-1 and -7 and neoplastic progression of HSCCs and LSCCs. Moreover, inverse shifts between nuclear and cytoplasmic positivity intimating functional divergence were detected.