Clinical features of oral lichen planus. A retrospective study of 65 cases

Objectives: To describe the clinical features of patients diagnosed with oral lichen planus (OLP) and to establish the prevalence of its malignant transformation in our setting. Study design: A retrospective study was made of 65 patients clinically and histologically diagnosed with OLP in the Service of Oral Surgery (Dental Clinic of the University of Barcelona, Spain) in the period 1990-2005. A descriptive and bivariate statistical analysis was made. Results: The mean patient age was 59 years (SD ± 14.9). Most of the patients (61%) were women, and the most frequent location of the lesions was the buccal mucosa (90.8%). White forms of OLP were noted in 66% of the cases, and 46.2% of the patients reported symptoms of some kind. The patients diagnosed with diabetes mellitus (20%) showed a larger proportion of red lesions (p=0.088). No statistically significant association was observed between chronic liver disease and the OLP lesion types or symptoms. Two cases of squamous cell carcinoma were identified in two patients previously or simultaneously diagnosed with OLP. A statistically significant correlation was observed between dysplastic changes / malignization of the lesions and smoking habit (p=0.019). An association to alcohol abuse was also noted, though in this case statistical significance was not reached (p=0.085). Conclusions: The clinical features of our study population were similar to those described in other studies. Diabetic patients with OLP were seen to be more susceptible to the development of atrophic-erosive lesions. Smokers and/or patients with alcohol abuse in turn showed a greater tendency to develop dysplastic changes / malignization in the histopathological study of the lesions

HPV & head and neck cancer: a descriptive update

The incidence of head and neck squamous cell carcinoma (HNSCC) has been gradually increasing over the last three decades. Recent data have now attributed a viral aetiology to a subset of head and neck cancers. Several studies indicate that oral human papillomavirus (HPV) infection is likely to be sexually acquired. The dominance of HPV 16 in HPV+ HNSCC is even greater than that seen in cervical carcinoma of total worldwide cases. Strong evidence suggests that HPV+ status is an important prognostic factor associated with a favourable outcome in head and neck cancers. Approximately 30 to 40% of HNSCC patients with present with early stage I/II disease. These patients are treated with curative intent using single modality treatments either radiation or surgery alone. A non-operative approach is favored for patients in which surgery followed by either radiation alone or radiochemotherapy may lead to severe functional impairment. Cetuximab, a humanized mouse anti-EGFR IgG1 monoclonal antibody, improved locoregional control and overall survival in combination with radiotherapy in locally advanced tumours but at the cost of some increased cardiac morbidity and mortality. Finally, the improved prognosis and treatment responses to chemotherapy and radiotherapy by HPV+ tumours may suggest that HPV status detection is required to better plan and individualize patient treatment regimes.

Salivary gland cancer in Finland: Incidence, histological distribution, outcome and prognostic factors

Salivary gland cancer (SGC) is a rare cancer. The histological classification of SGC is complex and its biological behavior highly variable: it may vary from a low-grade tumor to a high-grade and often fatal malignancy. These circumstances make this cancer a diagnostic and therapeutic challenge. Older age and exposure to ionizing radiation are known risk factors. The mainstay of treatment is surgery combined with adjuvant radiation therapy, when appropriate. In addition to the histological type, the only well known prognostic factor is the TNM classification, which describes the tumor size and the amount of metastases. This study was performed using a full population-based nationwide cohort of SGC patients and tumors diagnosed in Finland in 1991-1996. The annual incidence of SGC in the entire population was, on average, 47.7 per year. By histological re-evaluation of 237 specimens the most frequent histological types were the adenoid cystic carcinoma (n=65; 27%), the mucoepidermoid carcinoma (n=45; 19%) and the acinic cell carcinoma (n=41; 17%). The highest 10-year disease-specific survival rate occurred among patients with acinic cell carcinoma (90%), followed by mucoepidermoid carcinoma (81%) and adenoid cystic carcinoma (60%). A high volume-corrected index (VCI) of Ki-67 correlated with worse survival of patients with SGC. Computer-assisted morphometric analyses of CD34-positive vessels indicated an unfavorable prognosis for patients with mucoepidermoid carcinoma and an association with poor survival among patients with acinic cell carcinoma. A high level of expression of matrix metalloproteinase-9 (MMP-9) showed a trend for a poorer prognosis in salivary duct carcinoma, and a high level of MMP-13 and a low level of MMP-1 had a trend for a poorer prognosis of patients with SGC. A low level of MMP-7 was associated with a poor prognosis of patients with acinic cell and mucoepidermoid carcinoma.

Rastreamento de lesões pré-neoplásicas do ânus: citologia anal e anuscopia de alta resolução novas armas para prevenção

Squamous anal cell carcinoma frequency has been changing during the last decades. It was a rare disease in the past with 0.2 cases per 100,000 inhabitants in Denmark before the 60’s and 0.5 per 100,000 in the United States of America (USA) in 1973. Currently these figures have risen to a 1.00 / 100,000 ratio in accordance with the public records in the USA. Although the incidence in the general population can still be considered low, regardless of having doubled during the past 30 years, some specific groups in the population seem to have a higher level of risk, with a ratio of 70 ocurrences per each group of 100,000 individuals. The relationship between infections caused by oncogenic types of human papillomavirus and the similarity with cervical squamous cell carcinoma lead us to believe that screening techniques similar to the ones used as from the 40’s aiming the control of the cervical carcinoma, such as Papanicolaou smear (anal cytology) and colposcopy (high resolution anoscopy), may be effective on anal cancer prevention in those specific groups, or at least, to its early diagnosis. This article presents the techniques for tracking these early anal cancer lesions justifying them as a Public Health point of view.

Prevalence of alterations in chest computerized tomography in patients with head and neck cancer

Objective: to assess the prevalence of abnormalities found by computed tomography (CT) of the chest in patients with squamous cell carcinoma of the head and neck. Methods: we retrospectively analyzed chest CT exams of 209 patients with squamous cell carcinoma of the head and neck. The CT findings were stratified as inflammatory / infectious, parenchymal, nodular uncharacteristic and nodular metastatic / tumoral Results: alterations were diagnosed in 66.6% of patients. Of these, 25.3% represented emphysema; 18.8%, uncharacteristic micronodules; 12.9%, metastases; 11.9%, thoracic lymph node enlargements; and in 6.6% we detected active pulmonary tuberculosis or its sequelae, pneumonia or inflammatory / infectious signs and pleural thickening or effusion. Conclusion: the prevalence of exams with alterations and the considerable rate of detected metastases indicate that chest CT should be required for diagnostic and / or staging in cases of head and neck cancer.

Plastic surgery in chest wall reconstruction: relevant aspects - case series

Objective: to discuss the participation of Plastic Surgery in the reconstruction of the chest wall, highlighting relevant aspects of interdisciplinaryness. Methods: we analyzed charts from 20 patients who underwent extensive resection of the thoracic integument, between 2000 and 2014, recording the indication of resection, the extent and depth of the raw areas, types of reconstructions performed and complications. Results: among the 20 patients, averaging 55 years old, five were males and 15 females. They resections were: one squamous cell carcinoma, two basal cell carcinomas, five chondrosarcomas and 12 breast tumors. The extent of the bloody areas ranged from 4x9 cm to 25x40 cm. In 12 patients the resection included the muscular plane. In the remaining eight, the tumor removal achieved a total wall thickness. For reconstruction we used: one muscular flap associated with skin grafting, nine flaps and ten regional fasciocutaneous flaps. Two patients undergoing reconstruction with fasciocutaneous flaps had partially suffering of the flap, solved with employment of a myocutaneous flap. The other patients displayed no complications with the techniques used, requiring only one surgery. Conclusion: the proper assessment of local tissues and flaps available for reconstruction, in addition to the successful integration of Plastic Surgery with the specialties involved in the treatment, enable extensive resections of the chest wall and reconstructions that provide patient recovery.

Survival following orbital exenteration at a tertiary brazilian hospital

Objective: to analyze the epidemiology, clinical features and survival rate of patients undergoing orbital exenteration (OE) in a tertiary referral hospital. Methods : we conducted a retrospective study of all patients undergoing OE at the Hospital das Clínicas, FMUSP between January 2007 and December 2012. We collected data records related to gender, age, origin, length of stay, duration of the disease, other treatments related to the disease, number of procedures outside of the face related to the disease, follow-up and histological diagnosis. Results : we treated 37 patients in the study period. The average survival in one year was 70%, in two years, 66.1%, and 58.3% in three years. There was no significant difference in the one-year survival related to histological diagnosis (p=0.15), days of hospitalization (p=0.17), gender (p=0.43), origin (p=0.78), disease duration (p=0.27) or the number of operations for the tumor (p=0.31). Mortality was higher in elderly patients (p=0.02). The average years of life lost was 33.9 in patients under 60 years, 14.7 in patients in the 61-80 years range and 11.3 in patients over 80 years. Conclusion : the present series of cases is significant in terms of prevalence of orbital exenteration; on the other hand, it shows one of the lowest survival rates in the literature. This suggests an urgent need for improved health care conditions to prevent deforming, radical resections.

Histopathological aspects of Bovine Enzootic Hematuria in Brazil

The bladder lesions of 59 cattle, from the States of Rio de Janeiro, São Paulo, Minas Gerais, Espírito Santo, Rio Grande do Sul, Santa Catarina, Paraná and Amazon, affected by Bovine Enzootic Haematuria (BEH), were studied histologically. The objective of this study was to describe and reclassify neoplastic and non-neoplastic alterations not yet reported, according to the more complete current nomenclature used in human medicine. There was an almost complete identity with alterations observed in the bladder of man. Due to the occurrence of two or more neoplasms in the same animal, differences in the methodology and in the concept of classification, a more precise comparison was not possible. Coexistence of different types of epithelial and/or mesenchymal tumour growth was frequently seen. Rare neoplasms or differentiations not previously described were found in the bladder of some animals affected by BEH. These were trabecular carcinoma with Paneth cells differentiation, mesonephroid adenoma, mesonephroid adenocarcinoma, "signet ring" cell carcinoma, plasmocytoid carcinoma, chromophobe cell carcinoma and nested type of transitional cell carcinoma. Haemangiosarcomas originating from haemangiomas were also observed. This study also revealed the occurrence of many tumors with anaplasia and pronounced infiltrative features, but which did not metastasize. The elucidation of the cause of this "barrier against metastases" and its relationship with chemical carcinogenesis induced by the ptaquiloside, the active principle of bracken fern (Pteridium aquilinum), could be of interest to future research on the control ofneoplasia in man and animals.

Regulation of epidermal tight junctions by calcium ATPases and p38

The epidermis is the upper layer of the skin and keratinocytes are its most abundant cells. Tight junctions are cell junctions located in the granular layer of the epidermis. They maintain the polarity of the cells and regulate the movement of water-soluble molecules. Epidermal tight junctions may lose their integrity when there are defects in intercellular calcium regulation. Hailey-Hailey and Darier´s disease are dominantly inherited, blistering skin diseases. Hailey-Hailey disease is caused by mutations in the ATP2C1 gene encoding a calcium/manganese ATPase SPCA1 of the Golgi apparatus. Darier´s disease is caused by mutations in the ATP2A2 gene encoding a calcium ATPase SERCA2 of the endoplasmic reticulum. p38 regulates the differentiation of keratinocytes. The overall regulation of epidermal tight junctions is not well understood. The present study examined the regulation of tight junctions in the human epidermis with a focus on calcium ATPases and p38. Skin from Hailey-Hailey and Darier´s disease patients was studied by using immunofluorescence labeling which targeted intercellular junction proteins. Transepidermal water loss was also measured. ATP2C1 gene expression was silenced in cultured keratinocytes, by siRNA, which modeled Hailey-Hailey disease. Expression of intercellular junction proteins was studied at the mRNA and protein levels. Squamous cell carcinoma and normal human keratinocytes were used as a model for impaired and normal keratinocyte differentiation, and the role of p38 isoforms alpha and delta in the regulation of intercellular junction proteins was studied. Both p38 isoforms were silenced by adenovirus cell transduction, chemical inhibitors or siRNA and keratinocyte differentiation was assessed. The results of this thesis revealed that: i.) intercellular junction proteins are expressed normally in acantholytic skin areas of patients with Hailey-Hailey or Darier´s disease but the localization of ZO-1 expanded to the stratum spinosum; ii.) tight junction proteins, claudin-1 and -4, are regulated by ATP2C1 in non-differentiating keratinocytes; and iii.) p38 delta regulates the expression of tight junction protein ZO-1 in proliferating keratinocytes and in squamous cell carcinoma derived cells. ZO-1 silencing, however, did not affect the expression of other tight junction proteins, suggesting that they are differently regulated. This thesis introduces new mechanisms involved in the regulation of tight junctions revealing new interactions. It provides novel evidence linking intracellular calcium regulation and tight junctions.

Fifty years in the blink of an eye: a retrospective study of ocular and periocular lesions in domestic animals

A survey was undertaken aiming to obtain an overview of ocular and periocular lesions diagnosed in domestic mammals over a period of 50 years in a veterinary pathology diagnostic laboratory in the Central Region of the State of Rio Grande do Sul, Brazil. In this lab, 33,075 histophatological exams had been performed over the period surveyed, of which 540 (1.6%) concerned ocular and periocular lesions. For various reasons ninety specimens were excluded from the study and the remaining 450 consisted of samples from dogs (53.5%), cattle (28.2%), cats (11.1%), horses (5.1%) sheep (1.3%), rabbits (0.4%), and pig (0.2%). The eyelids were the most prevalent (248/450) site of lesions in each of the species studied, followed by third eyelid (73/450), and conjunctiva (27/450). In dogs (241 samples) lesions in sebaceous glands (including Meibomian glands) were the most common findings (75/241), followed by melanocytic tumors (52/241) and nonspecific conjunctivitis (13/241). Squamous cell neoplasms, both benign and malignant, were relatively common. In cattle, anatomical sites affected by ocular and periocular lesions, in decreasing order of frequency, were eyelid, cornea and third eyelid. Squamous cell carcinoma (SCC) alone accounted for 80.3% of all diagnoses, while all neoplastic lesions made up for 85.0% of the lesions diagnosed in cattle. Neoplasia accounted for most of the lesions diagnosed in cats (39/50 cases); all of these were malignant, and SCC, hemangiosarcoma and fibrosarcoma were the most common types diagnosed. In horses, 19 out of 23 submissions were neoplasms and most were sarcoid (8/23) and SCC (8/23). There were six submissions from sheep with unpigmented skin, all of which represented SCC of the eyelids (5) and third eyelid (1).

Genetic susceptibility to HPV infection and cervical cancer

Squamous cell carcinoma of the cervix (SCCC) is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HPV) is the major risk factor to develop malignant lesions in the cervix. Polymorphisms of the MHC and p53 genes seem to influence the outcome of HPV infection and progression to SCCC, although controversial data have been reported. MHC are highly polymorphic genes that encode molecules involved in antigen presentation, playing a key role in immune regulation, while p53 is a tumor suppressor gene that regulates cell proliferation. The HPV E6 protein from high-risk types binds p53 and mediates its degradation by the ubiquitin pathway. The role of these polymorphisms in genetic susceptibility to HPV infection and to SCCC remains under investigation.

No evidence for mutations in exons 1, 8 and 18 of the patched gene in sporadic skin lesions of Brazilian patients

There is strong evidence that the patched (PTCH) gene is a gene for susceptibility to the nevoid basal cell carcinoma syndrome. PTCH has also been shown to mutate in both familial and sporadic basal cell carcinomas. However, mutations of the gene seem to be rare in squamous cell carcinomas. In order to characterize the role of the gene in the broader spectrum of sporadic skin malignant and pre-malignant lesions, we performed a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of genomic DNA extracted from 105 adult patients (46 females and 59 males). There were 66 patients with basal cell carcinomas, 30 with squamous cell carcinomas, 2 with malignant melanomas and 7 patients with precancerous lesions. Two tissue samples were collected from each patient, one from the central portion of the tumor and another from normal skin. Using primers that encompass the entire exon 1, exon 8 and exon 18, where most of the mutations have been detected, we were unable to demonstrate any band shift. Three samples suspected to present aberrant migrating bands were excised from the gel and sequenced directly. In addition, we sequenced 12 other cases, including tumors and corresponding normal samples. A wild-type sequence was found in all 15 cases. Although our results do not exclude the presence of clonal alterations of the PTCH gene in skin cancers or mutations in other exons that were not screened, the present data do not support the presence of frequent mutations reported for non-melanoma skin cancer of other populations.

Formin proteins in normal tissues and cancer

The actin cytoskeleton is a dynamic structure that determines cell shape. Actin turnover is mandatory for migration in normal and malignant cells. In epithelial cancers invasion is frequently accompanied by epithelial to mesenchymal transition (EMT). In EMT, cancer cells acquire a migratory phenotype through transcriptional reprogramming. EMT requires substantial re-organization of actin. During the past decade, new actin regulating proteins have been discovered. Among these are members of the formin family. To study formin expression in tissues and cells, antibodies for detection of formin proteins FMNL1 (Formin-like protein 1), FMNL2 (Formin-like protein 2) and FHOD1 (Formin homology 2 domain containing protein 1) were used. The expression of formins was characterized in normal tissues and selected cancers using immunohistochemistry. The functional roles of formins were studied in cancer cell lines. We found that FMNL2 is widely expressed. It is a filopodial component in cultured melanoma cells. In clinical melanoma, FMNL2 expression has prognostic significance. FHOD1 is a formin expressed in mesenchymal cell types. FHOD1 expression is increased in oral squamous cell carcinoma (SCC) EMT. Importantly, FHOD1 participates in invasion of cultured oral SCC cells. FMNL1 expression is low in normal epithelia, but high in leukocytes and smooth muscle cells. Expression of FMNL1 can be found in carcinoma; we detected FMNL1 expressing cells in basal type of breast cancer. Our results indicate that formins are differentially expressed in normal tissues and that their expression may shift in cancer. Functionally FMNL2 and FHOD1 participate in processes related to cancer progression. Studying formins is increasingly important since they are potential drug targets.

CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95% CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95% CI = 0.70-2.79) with OSCC.

Genetic variability of vascular endothelial growth factor and prognosis of head and neck cancer in a Brazilian population

Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis. Polymorphisms in this gene have been evaluated in patients with several types of cancer. The objectives of this study were to determine if there was an association of the -1154G/A polymorphism of the VEGF gene with head and neck cancer and the interaction of this polymorphism with lifestyle and demographic factors. Additionally, the distribution of the VEGF genotype was investigated with respect to the clinicopathological features of head and neck cancer patients. The study included 100 patients with histopathological diagnosis of head and neck squamous cell carcinoma. Patients with treated tumors were excluded. A total of 176 individuals 40 years or older were included in the control group and individuals with a family history of neoplasias were excluded. Analysis was performed after extraction of genomic DNA using the real-time PCR technique. No statistically significant differences between allelic and genotype frequencies of -1154G/A VEGF polymorphism were identified between healthy individuals and patients. The real-time PCR analyses showed a G allele frequency of 0.72 and 0.74 for patients and the control group, respectively. The A allele showed a frequency of 0.28 for head and neck cancer patients and 0.26 for the control group. However, analysis of the clinicopathological features showed a decreased frequency of the A allele polymorphism in patients with advanced (T3 and T4) tumors (OR = 0.36; 95%CI = 0.14-0.93; P = 0.0345). The -1154A allele of the VEGF gene may decrease the risk of tumor growth and be a possible biomarker for head and neck cancer. This polymorphism is associated with increased VEGF production and may have a prognostic importance.