Oral amyloidosis: an update.

BACKGROUND: Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors. MATERIAL AND METHODS: Electronic searches were undertaken in five databases supplemented by manual scrutiny. RESULTS: A total of 111 studies were included with 158 individuals. CONCLUSIONS: The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.

MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study.

BACKGROUND: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSß (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. MATERIAL AND METHODS: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSßhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. RESULTS: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. CONCLUSIONS: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT.

HIV-related non-Hodgkin lymphomas affecting the oral cavity: a clinicopathologic study of 11 cases.

BACKGROUND: HIV-related non-Hodgkin lymphomas of the oral cavity are rare lesions with aggressive clinical behaviour. The aim of this study is to describe the clinicopathological features of a series of HIV-related oral non-Hodgkin lymphomas. MATERIAL AND METHODS: Eleven cases of oral lymphomas affecting HIV-positive patients were retrieved from 2012 to 2019. Clinicopathological features regarding age, sex, tumour location, clinical presentation, laboratory findings, disease stage and follow-up were obtained. Histologic, immunohistochemical and in situ hybridization for EBV detection were done for diagnosis confirmation. Overall survival was estimated by Kaplan-Meier curve. RESULTS: Males predominated, with a mean age of 40.3 years-old. Maxilla and mandible were the mostly affected. Plasmablastic lymphoma and diffuse large B-cell lymphoma not otherwise specified (NOS) were the main histological types. Lesions presented as reddish ulcerated swellings, representing the first sign of AIDS in six cases. Stage IV were common (7 cases) and the mean HIV viral load was 10,557 copies/mL, with a mean of 266 CD4+ cells/mm3, 1,278 CD8+ cells/mm3 and a CD4+/CD8+ ratio of 0.26. Eight patients died of the disease (72.7%). Overall survival revealed that 78.2% of the patients died after 21 months of follow-up. CONCLUSIONS: HIV-related oral lymphomas present a poor prognosis usually diagnosed in advanced stages and in our series plasmablastic lymphoma was the most common subtype.

Salivary gland cancer in Southern Brazil: a prognostic study of 107 cases.

BACKGROUND: Salivary gland cancers (SGC) represent an uncommon group of heterogeneous tumors. We performed a retrospective survey of SGC diagnosed in a reference center for treatment of malignant tumors from the south of Brazil aiming to determine the prognostic value of demographic, clinic and pathologic features. MATERIAL AND METHODS: Cases diagnosed as SGC between 2006 and 2016 were retrospectively collected. Medical records were examined to extract demographic, clinic, pathologic and follow-up information. RESULTS: One-hundred and seven cases of SGC were identified. The most common SGC were mucoepidermoid carcinoma (MEC) (n = 39) followed by adenoid cystic carcinoma (AdCC) (n = 29). Among AdCCs, 55.2% of cases were classified as cribriform, 27.6% as tubular and 17.2% as solid. The tubular subtype had the highest percentage of cases with perineural invasion (p=0.01). Among MEC, 61.5% of cases were classified as low grade, 15.4% as intermediate grade and 19.9% as high grade. Low grade MEC had the lowest percentage of cases with perineural invasion (p=0.04). The 5-year survival for loco-regional control, disease-free survival (DFS) and disease-specific survival were 75%, 70% and 84%, respectively. The following features were associated with poor DFS: advanced age (p=0.03), rural residency (p=0.01), being a smoker or former smoker (p=0.01), pain (p=0.03), nodal metastasis (p<0.001), need for chemotherapy (p=0.02), neck dissection (p=0.04), perineural invasion (p=0.01), and being diagnosed with AdCC compared to MEC (p=0.02). CONCLUSIONS: The clinco-demographic and pathologic features identified as prognostic factors reveal the profile of patients at increased risk of recurrence and who would benefit from closer follow-up.

Malignant transformation of oral leukoplakia: a multicentric retrospective study in Brazilian population.

BACKGROUND: Among the oral potentially malignant disorders, leukoplakia stands out as the most prevalent. The purpose of this study was to analyse the clinical-pathological features of oral leukoplakia in groups of patients from three major pathology centers in two different regions of Brazil, in order to determine which factors would be associated to the clinical risk of malignant transformation. MATERIAL AND METHODS: A total of 148 patients was analyzed, and data regarding gender, age, site, classification of the clinical subtype, harmful habits such as use of tobacco and alcohol, time of evolution and presence of dysplasia were collected. The association between risk factors and malignant transformation was investigated using the chi-square test and Fischer's exact test for correlation of variables. A significance level of 5% (p≤0.05) was used. RESULTS: The mean age of the patients was 60 years, and 56% were female. Most of the lesions (34,5%) were located in the lateral and ventral regions of the tongue. Of the 148 patients, ninety had clinical follow-up. Malignant transformation occurred in 13 patients (8.8%), with an average of 44 months of follow up. CONCLUSIONS: Non-smoker, nonhomogeneous clinical presentation, location at the tongue, and the presence of high degree of dysplasia were statistically relevant factors associated with a higher risk of transformation transformation.

CD1a+ and CD207+ cells are reduced in oral submucous fibrosis and oral squamous cell carcinoma.

BACKGROUND: The objective of this study investigated the distribution of immature dendritic cells (DCs), Langerhans cells and plasmacytoid DCs in oral submucous fibrosis (OSMF), OSMF associated with oral squamous cell carcinoma (OSMF-OSCC), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Fourteen cases of OSMF, 9 of OSMF-OSCC, 8 of OL¸ 45 of OSCC and 8 of normal epithelium were retrospectively retrieved and their diagnoses confirmed. Immunoreactions against CD1a, CD207 e CD303 were performed and the number of positive cells quantified. RESULTS: A significant decrease of CD1a+ was found in OSMF (p≤0.05), OSMF-OSCC (p ≤ 0.01), and OSCC (p ≤ 0.001) when compared to normal epithelium. For CD207+ the significance decrease was observed in OSMF-OSCC (p ≤ 0.05), and OSCC (p ≤ 0.01) when compared with normal epithelium, and in OSMF when compared with OL (p ≤ 0.05). There was no significant difference for CD303, but increased in CD303+ was observed in OSCC when compared with normal epithelium. CONCLUSION: The decrease in the number of CD1a+ and CD207+ cells may be associate to the development of oral OSCC, and in OPMDs they might be indicators of malignant transformation.

Sinonasal melanoma: a systematic review of the prognostic factors.

The objective was to evaluate the available published data on sinonasal melanoma and analyse its clinical features, treatment modalities, and prognostic factors. An electronic search was undertaken in March 2018 in multiple databases. Eligibility criteria included publications with sufficient clinical, histological, and immunohistochemical information to confirm the diagnosis. Seventy-three publications (439 cases) were included. The lesion was more prevalent in females than in males. There was a higher prevalence in the seventh and eighth decades of life. The lesions mainly presented as epistaxis and commonly involved the nasal cavity. Age (>67.6 years; P=0.0012), primary location (middle turbinate; P=0.0112), disease stage (advanced disease stage; P=0.0026), treatment (radiotherapy; P=0.0111), recurrence (recurrence presented; P=0.0137), and distant metastasis (distant metastasis presented; P=0.0011) were independently associated with a lower survival rate. Recurrence was significantly correlated with age (>67.6 years; P=0.0021), sex (males tended to present a higher recurrence rate than females; P=0.0051), disease stage (stages III and IV presented a higher recurrence rate than stages I and II; P=0.0331), and histological type (amelanotic lesions presented a higher index of recurrence than melanotic lesions; P=0.0095). In conclusion, sinonasal melanoma is a neoplasm with a poor prognosis, presenting a 30.69% possibility of survival after 5 years.

Benign epithelial oral lesions - association with human papillomavirus.

BACKGROUND: The presence of human papilloma virus in benign oral lesions has been studied by different techniques obtaining extremely variable results. The objective of this study was to determine the presence of human papillomavirus in 83 cases of benign hyperplastic epithelial oral lesions. MATERIAL AND METHODS: Eighty-three oral lesions with clinical or histopathological features suggestive of HPV infection were retrieved from the files of four oral pathology services. Demographic data were obtained from patient's medical charts. All cases had available clinical image, H&E preparations and paraffin blocks with enough tissue for HPV detection by in situ hybridization, and immunohistochemical reactions for Ki67. RESULTS: Episomal positivity for wide spectrum HPV was observed in 24% of the cases; most of them (70%) HPV 6/11 positive. HPV 16/18 was not detected. Condyloma acuminatum was the most common lesion associated with HPV (75%), followed by verruca vulgaris (15%), squamous papilloma and multifocal epithelial hyperplasia, 5% each. Koilocytes were identified in all the HPV positive cases. Ki67 showed an abnormal proliferation pattern in 90% of the HPV positive cases; most of them (70%) showing groups of proliferating cells in focal superficial regions, and in 20% positivity was seen almost in the whole thickness of the epithelium. HPV negative cases showed Ki67 positive cells restricted to the basal layer. CONCLUSIONS: Regarding oral lesions associated with HPV, condyloma is the most common lesion expressing low-risk subtypes. The etiology of squamous papilloma remains controversial as HPV was found in 1.9% of the cases. The identification of koilocytes and the pattern of expression of Ki67 reflect HPV infection and are helpful for classification. Papillary oral lesions not associated to HPV deserve further studies to better clarify its etiology.

Chondrosarcoma of the jaw bones: a review of 224 cases reported to date and an analysis of prognostic factors.

The objective was to integrate the available published data on chondrosarcoma (CHS) of the jaw bones into a comprehensive analysis of its clinical and histological features, treatment, and prognostic factors. An electronic search was undertaken in October 2017. To be eligible, the publication had to provide sufficient clinical/histological data to confirm the diagnosis. One hundred and ten publications (224 cases of CHS) were identified and included. There was a slightly higher prevalence of CHS in males than in females. Most subjects with CHS were in the second to fifth decades of life. The most common symptom was swelling and the most commonly observed location was the maxilla. Histologically, most tumours were of the conventional type and were low grade tumours. The treatment of choice was tumour resection. Histological grade, treatment with chemotherapy alone, and the presentation of recurrence or metastasis were found to be significant independent prognostic factors: patients who presented high-grade tumours, who received chemotherapy alone as the treatment of choice, and those who presented recurrence or metastasis were more likely to have a worse prognosis. In addition, radical surgery associated with radiotherapy as the treatment protocol showed a better prognosis.

Clinicopathological analysis of head and neck rhabdomyosarcoma: A series of 10 cases and literature review.

BACKGROUND: To describe the clinicopathological characteristics of a series of head and neck rhabdomyosarcoma (RMS) and to review the literature. MATERIAL AND METHODS: Cases diagnosed as RMS affecting the head and neck region were retrospectively retrieved from the files of two Brazilian institutions from January 2006 to January 2017. Data on clinical features (sex, age and affected site), microscopic subtype, immunohistochemical results, treatment employed and follow-up status were obtained from the patient's medical charts. RESULTS: During the period considered, 10 cases of RMS were identified. Females predominated (4M:6F), the mean age at diagnosis was 16.5 years-old and the orbit was the most affected site (4 cases). Microscopically, most cases were classified as embryonal RMS (6 cases) and the Desmin/Myogenin/Myo-D1 immunohistochemical positivity was useful to confirm the diagnosis. Chemotherapy and radiotherapy were applied to 9 and 8 patients respectively, whereas 2 patients were treated by surgery. Recurrences occurred in 3 patients and distant metastasis in 2 cases. Nine patients were alive in their last follow-up, 3 of them with disease, whereas 1 patient died due to the disease. CONCLUSION: Head and neck RMS is an aggressive malignant neoplasm which demands especial concern to achieve early diagnosis and successful treatment.

Risk of damage and mortality in SLE patients fulfilling the ACR or only the SLICC classification criteria. A 10-year, inception cohort study.

Objective To compare damage and mortality, from inception up to 10-year follow-up, between SLE patients meeting at baseline the 1997 ACR criteria or only the 2012 SLICC classification criteria. Methods Patients fulfilling the ACR and/or the SLICC classification criteria for SLE were enrolled at inception and followed-up to 10 years at an academic lupus clinic. Damage was defined as SLICC Damage Index (SDI) score ≥1. We assessed with multivariate Cox models the damage and mortality outcomes, according to SLE classification status at inception, adjusting for potential baseline confounders. Results We recruited 192 patients (69.8% fulfilling at inception the ACR criteria and 30.2% only the SLICC criteria). During follow-up, 24.0% of patients accrued organ damage and 4.2% died. Patients meeting ACR criteria compared to those with SLICC criteria alone presented during follow-up with more cases of lupus nephritis (35.1% versus 13.8%, p < 0.01), but less thrombotic antiphospholipid syndrome (4.5% versus 17.2%, p < 0.01). The Cox models showed no significant differences in risk for damage [hazard ratio (HR) (95% CI) 0.991 (0.453-2.167)] or death [hazard ratio (HR) (95% CI) 0.694 (0.107-4.506)] between groups. Conclusion The SLE classification status at inception identified different patterns of clinical phenotype, but did not influence damage accrual or mortality up to 10-year follow-up.

Clinical and genetic analysis of patients with cherubism.

OBJECTIVE: To describe the clinical and genetic features of patients with cherubism. MATERIAL AND METHODS: A descriptive analysis of 14 cases from nine different families was carried out. Clinicopathological, imaging, and follow-up data were retrieved from patients' medical files and correlated with the genetic profile of each patient. Genomic DNA isolated from buccal mucosa cells was subjected to direct sequencing analysis of the SH3BP2 gene. RESULTS: Females were more affected than males (8:6), and the mean age at diagnosis was 8.6 years (range 3-30 years). Eleven patients exhibited simultaneous bilateral involvement of the maxilla and mandible. Two patients did not have a familial history of cherubism. Progressive growth pattern was found in six patients and stable lesions were observed in other seven patients, whereas in one patient, complete spontaneous remission was documented during the follow-up (31 years). Mutations were found in 13 cases and included the typical heterozygous missense mutations R415Q, P418T, and P418H at exon 9 of SH3BP2. No correlation between the mutations and the clinical manifestations was observed. CONCLUSION: Three different point mutations in the SH3BP2 gene were detected with variable clinical involvement. Genotype-phenotype association studies in larger population with cherubism are necessary to provide important knowledge about molecular mechanisms related to the disease.

Gingival granulomatosis with polyangiitis (Wegener's granulomatosis) as a primary manifestation of the disease.

Granulomatosis with polyangiitis (GPA) is a potentially lethal disease characterized by systemic necrotizing vasculitis, which affects small- and medium-sized blood vessels and is often associated with serum cytoplasmic antineutrophil cytoplasmic antibody. The upper and lower respiratory tract and kidney are the most involved sites, but oral lesions can be identified in 6-13% of the cases, whereas in only 2% of the cases, oral manifestations represent the first signal of the disease usually as gingival swellings or unspecific ulcerations. Without treatment, the mainstay of which is the combination of immunosuppressants and systemic corticosteroids, GPA may run a fatal course. In this report we describe an original case of GPA affecting a 75-year-old female patient referred to our service due to a gingival swelling with 3-month duration. Although the patient was correctly diagnosed and promptly treated, she died 3 months after the initial diagnosis.

Clinicopathological prognostic factors of oral tongue squamous cell carcinoma: a retrospective study of 202 cases.

Although several histopathological parameters and grading systems have been described as predictive of the treatment response and outcome of oral squamous cell carcinoma (OSCC), none is universally accepted. A new scoring system, the histological risk model, was recently described to be a powerful predictive tool for recurrence and overall survival in OSCC. The aim of this study was to verify the predictive role of the histological risk model in a cohort of 202 patients at all stages of oral/mobile tongue squamous cell carcinoma (OTSCC). Demographic and clinical data were collected from the medical records and the tumours were evaluated using the histological risk model. Statistical analyses were performed using the χ(2) test, the Kaplan-Meier method, and the Cox regression model. The histological risk model showed no statistical correlation with demographic or clinical parameters and did not Predict the outcome of the OTSCC patients. However, multivariate regression analysis revealed a significant correlation of the clinical disease stage with the disease outcome. Despite major efforts to identify new predictive parameters and histological systems, clinical features are still the most reliable prognostic factors for patients with OTSCC.

Expression analysis of thrombospondin 2 in prostate cancer and benign prostatic hyperplasia.

Thrombospondin 2 (TSP2) is a protein with important roles in different tumor types, mainly related to tumor inhibition. However, there are limiting data regarding TSP2 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH). We aimed to investigate TSP2 transcript and protein expression in tumoral and non-tumoral prostate tissues and cell lines, and its implications for PCa diagnosis and progression. TSP2 transcript expression was evaluated by real time PCR in PCa and BPH tissue samples and in tumoral and non-tumoral cell lines. TSP2 protein expression analysis was conducted by immunohistochemistry in a tissue microarray (TMA) containing PCa and BPH tissue samples. TSP2 transcript was down-regulated in PCa tissue samples and cell lines, when compared to BPH and non-tumoral samples (P<0.01). Receiver Operating Curve (ROC) analysis demonstrated that TSP2 transcript levels can better distinguish PCa from BPH tissue samples (P<0.01) than serum PSA levels (P=0.299). TSP2 protein expression has been observed in the cytoplasm of both PCa and BPH epithelial and stromal compartments. TSP2 stromal staining scores were significantly lower in PCa than in BPH tissues (P<0.01), while similar TSP2 epithelial staining patterns were observed in both diseases. Notably, the TSP2 epithelial staining score was significantly correlated to vascular invasion and biochemical recurrence in PCa tissue samples (P<0.05). Our data indicate that TSP2 is down-regulated at PCa tissues and cell lines, especially at stroma compartment, which could be related to PCa progression. TSP2 levels could potentially be applied for differential PCa and BPH diagnosis.

Clinicopathological analysis of head and neck chondrosarcoma: three case reports and literature review.

Chondrosarcoma (CHS) is a malignant neoplasm characterized by the formation of cartilaginous matrix by neoplastic cells, with a high propensity for local recurrences. Head and neck CHS is rare, accounting for less than 12% of all cases of CHS, usually affecting the maxilla. The majority of affected patients are in the fourth decade of life, with a slight predilection for male patients. A painless swelling is commonly the most frequent complaint. Surgery with wide en-bloc resection is the preferred treatment for CHS; radiotherapy and chemotherapy are usually palliative options. Owing to its rarity, there are few clinical series evaluating the biological behaviour of head and neck CHS. The aim of this study is to analyse the clinicopathological characteristics of head and neck CHS by reporting 3 new cases of this neoplasia affecting the jaw bones and reviewing the clinical series previously published in the English literature.

Microbial diversity in the larval gut of field and laboratory populations of the sugarcane weevil Sphenophorus levis (Coleoptera, Curculionidae).

The sugarcane weevil, Sphenophorus levis, is a wide-spread sugarcane pest in Brazil. Sphenophorus levis may depend on microorganisms that inhabit its intestinal tract. We examined the diversity of the gut microbiota of S. levis, which was characterized using culture-dependent and culture-independent methods. Analysis of 16S rRNA amplified directly from the gut community revealed the presence of 14 genera, one group from the Candidatus category, one uncultured group assigned to the family Flavobacteriaceae, and one uncultured group assigned to the family Enterobacteriaceae; all of them are members of the Alpha-Proteobacteria, Beta-Proteobacteria, Gamma-Proteobacteria, Firmicutes, and Bacteroidetes phyla. Microorganisms isolated through culture-dependent methods were classified according to morphological parameters and by 16S rRNA gene sequences. In addition to bacteria, four filamentous fungi were isolated. A higher bacterial diversity was observed in field populations of larvae than in laboratory populations, according to the Shannon index (Field H' = 3.36; Laboratory H' = 3.26). Five genera of bacteria and two filamentous fungi were found to have cellulolytic activity. This is the first report of S. levis gut microbiota; it may contribute to development of strategies for controlling this sugarcane pest.

Metallothionein and p-Akt proteins in oral dysplasia and in oral squamous cell carcinoma: an immunohistochemical study.

BACKGROUND: Oral leukoplakia (OL) is the main potentially malignant lesion of the oral cavity, and oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of p-Akt and Metallothionein (MT) proteins in dysplasic and neoplasic oral lesions. METHODS: Immunohistochemical studies were carried out on 10 normal epithelium, 30 OL and 15 OSCC paraffin-embedded samples. Immunoperoxidase reaction for p-Akt and MT proteins was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. RESULTS: Using the ANOVA and the Tukey's post hoc statistical analyses, it was observed a significant difference in the immunoexpression for p-Akt and MT when the OSCC samples were compared with normal and dysplasic epithelial groups. In addition, the Pearson's correlation test showed a significant correlation between the proteins' expression. CONCLUSION: Based on the data obtained, p-Akt and MT activation may play an important role in the conversion of a potentially malignant oral lesion to a malignant carcinoma since its earlier stages.

Does psychosocial stress cause hypertension? A systematic review of observational studies.

Acute stress promotes transient elevation of blood pressure, but there is no consistent evidence that this effect results in hypertension. In this systematic review of cohort and case-control studies that investigated the association between psychosocial stress and hypertension, we conducted a complete search up to February 2007 in MEDLINE, EMBASE, PSYCINFO and LILACS, through a search strategy that included eight terms to describe the exposure, six related to the design of the studies and one term for outcome. The quality was assessed by the Newcastle-Ottawa Quality Assessment Scale. The selection was done in duplicate by two teams of independent reviewers. Among 82 studies selected in the second phase, only 14 (10 cohort studies and 4 case-control studies), totalling 52,049 individuals, fulfilled the selection criteria. The average quality of the studies was 6.6+/-1.3 in a 9-point scale. Acute life events were associated with hypertension in one and were not associated in two studies. Five out of seven studies found a significant and positive association between measures of chronic stress and hypertension, with risk ratios ranging from 0.8 to 11.1. Three out of five studies reported high and significant risks of affective response to stress for hypertension, one a significant risk close to a unit and one reported absence of risk. Acute stress is probably not a risk factor for hypertension. Chronic stress and particularly the non-adaptive response to stress are more likely causes of sustained elevation of blood pressure. Studies with better quality are warranted.

FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome.

This study examines the clinical impact of PTEN genomic deletions using fluorescence in situ hybridisation (FISH) analysis of 107 prostate cancers, with follow-up information covering a period of up to 10 years. Tissue microarray analysis using interphase FISH indicated that hemizygous PTEN losses were present in 42/107 (39%) of prostatic adenocarcinomas, with a homozygous PTEN deletion observed in 5/107 (5%) tumours. FISH analysis using closely linked probes centromeric and telomeric to the PTEN indicated that subband microdeletions accounted for approximately 70% genomic losses. Kaplan-Meier survival analysis of PTEN genomic losses (hemizygous and homozygous deletion vs not deleted) identified subgroups with different prognosis based on their time to biochemical relapse after surgery, and demonstrated significant association between PTEN deletion and an earlier onset of disease recurrence (as determined by prostate-specific antigen levels). Homozygous PTEN deletion was associated with a much earlier onset of biochemical recurrence (P=0.002). Furthermore, PTEN loss at the time of prostatectomy correlated with clinical parameters of more advanced disease, such as extraprostatic extension and seminal vesicle invasion. Collectively, our data indicates that haploinsufficiency or PTEN genomic loss is an indicator of more advanced disease at surgery, and is predictive of a shorter time to biochemical recurrence of disease.