Prognostic implications of markers of the metabolic phenotype in human cutaneous melanoma.

BACKGROUND: Reprogramming of energy metabolism to enhanced aerobic glycolysis has been defined as a hallmark of cancer. OBJECTIVES: To investigate the role of the mitochondrial proteins, ß-subunit of the H+ -ATP synthase (ß-F1-ATPase), and heat-shock protein 60 (HSP60), and the glycolytic markers, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as the bioenergetic cellular (BEC) index, in melanoma progression. MATERIALS AND METHODS: The expression of energy metabolism proteins was assessed on a set of different melanoma cells representing the natural biological history of the disease: primary cultures of melanocytes, radial (WM35) and vertical (WM278) growth phases, and poorly (C81-61-PA) and highly (C8161-HA) aggressive melanoma cells. Cohorts of 63 melanocytic naevi, 55 primary melanomas and 35 metastases were used; and 113 primary melanoma and 33 metastases were used for validation. RESULTS: The BEC index was significantly reduced in melanoma cells and correlated with their aggressive characteristics. Overexpression of HSP60, GAPDH and PKM2 was detected in melanoma human samples compared with naevi, showing a gradient of increased expression from radial growth phase to metastatic melanoma. The BEC index was also significantly reduced in melanoma samples and correlated with worse overall and disease-free survival; the multivariate Cox analysis showed that the BEC index (hazard ratio 0·64; 95% confidence interval 0·4-1·2) is an independent predictor for overall survival. CONCLUSIONS: A profound alteration in the mitochondrial and glycolytic proteins and in the BEC index occurs in the progression of melanoma, which correlates with worse outcome, supporting that the alteration of the metabolic phenotype is crucial in melanoma transformation.

Biological markers of cisplatin resistance in advanced testicular germ cell tumours

INTRODUCTION: Germ cell tumours (GCTs) of the testis show exquisite sensitivity to treatment with cisplatin. Despite the high cure rates provided by platinum-based chemotherapy, 10-20% of patients die from progressive disease. Although various cellular pathways may influence cisplatin efficacy, their actual impact has not been comprehensively investigated in advanced GCTs. The objective of the present study was to clarify the role of the expression status of proteins involved in the Rb and p53 tumour suppressor pathways in sensitivity and resistance of GCTs to cisplatin-based chemotherapy. MATERIALS AND METHODS: Paraffin-embedded tumour tissues from 84 patients with advanced GCT treated with cisplatin-based chemotherapy were analysed. Immunohistochemical expression of proteins p53 and mdm2, and the G1-phase cyclins D1 and D2 (CD1 and CD2) was assessed and correlated with the clinical course. RESULTS: The percentages of positive expression of p53, mdm2, CD1 and CD2 were 56, 57, 37.5 and 55%, respectively. From univariate analysis, there was no significant association between p53, mdm2 or CD1 expression and outcome. Instead, positive CD2 expression was found to be marginally associated with shorter median duration of progression-free survival (PFS) (p=0.06). In multivariate analysis, none of the molecular markers retained statistical significance with treatment response or survival. CONCLUSIONS: Tissular expression of p53, mdm2 and CD1 is not associated with prognosis or treatment response in patients with advanced GCT. Aberrant CD2 expression appears to further determine a shorter PFS. Larger and further studies are required to validate CD2 as a marker of cisplatin resistance (AU)

Expression of EGFR, HER-2/neu and KIT in germ cell tumours

BACKGROUND: Germ cell tumours (GCTs) represent an extraordinarily chemosensitive malignancy. However, 20-30% of patients with advanced disease cannot be cured by currently available treatments. The role of tyrosine kinase receptors has been widely studied in other malignancies. Yet, limited information is available on GCTs. METHODS: One hundred and nine paraffin-embedded GCTs in 84 patients were assessed by immunohistochemistry for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2)/neu and KIT (CD117) expression. Univariate and multivariate analyses were performed to evaluate their role as predictive and/or prognostic factors. RESULTS: EGFR and HER-2/neu staining was detected in 28% and 13% of tumours, respectively, predominantly in nonseminomatous GCTs. KIT protein was almost universally expressed in seminomas (97%), being virtually absent in choriocarcinoma and teratocarcinoma subtypes. EGFR expression showed inverse association with tumour response of borderline significance. With a median follow-up of 10.6 years, no significant association was observed between the expression of any of these markers and relapse-free or overall survival. CONCLUSIONS: EGFR, HER-2/neu and KIT have differential patterns of expression in GCTs according to histological subtypes. The expression of these markers in our series had no prognostic or predictive significance (AU)

Chronic intestinal pseudo-obstruction: a diagnosis to be considered.

Chronic intestinal pseudoobstruction (CIPO) is a rare entity characterized by recurrent clinical episodes of intestinal obstruction in which no mechanical cause is identified. There are multiple causes for this syndrome but two main groups can be distinguished: a) secondary to a systemic non-gastrointestinal disease; and b) primary or idiopathic originated from alterations in the components of the intestinal wall. The latter forms are the most uncommon and their diagnosis is generally difficult. In the present article, we describe nine patients with CIPO that were diagnosed in our center over the last six years. Four of them were diagnosed with primary or idiopathic form of CIPO and another four were clearly secondary to a systemic disease. The ninth case, which was initially diagnosed as secondary, is probably also a primary form of the disease. The number of patients diagnosed in our center, even thought small, makes us to hypothesize that the prevalence of CIPO is probably greater than is generally believed and that the reasons of its rarity are the incomplete understanding of its physiopathology and the difficulties to achieve a correct diagnosis.

Chronic intestinal pseudo-obstruction: a diagnosis to be considered

Chronic intestinal pseudoobstruction (CIPO) is a rare entitycharacterized by recurrent clinical episodes of intestinal obstructionin which no mechanical cause is identified. There are multiplecauses for this syndrome but two main groups can be distinguished:a) secondary to a systemic non-gastrointestinal disease;and b) primary or idiopathic originated from alterations in thecomponents of the intestinal wall. The latter forms are the mostuncommon and their diagnosis is generally difficult. In the presentarticle, we describe nine patients with CIPO that were diagnosedin our center over the last six years. Four of them were diagnosedwith primary or idiopathic form of CIPO and another four wereclearly secondary to a systemic disease. The ninth case, whichwas initially diagnosed as secondary, is probably also a primaryform of the disease. The number of patients diagnosed in our center,even thought small, makes us to hypothesize that the prevalenceof CIPO is probably greater than is generally believed andthat the reasons of its rarity are the incomplete understanding ofits physiopathology and the difficulties to achieve a correct diagnosis(AU)

Primary extragastrointestinal stromal tumors in the omentum and mesentery: a clinicopathological and immunohistochemical study.

BACKGROUND/AIMS: This study aimed to describe the clinical, histological and immunohistochemical characteristics of primary extragastrointestinal stromal tumors (EGISTs) of the omentum and mesentery diagnosed in the Hospital 12 de Octubre, in Madrid, Spain, from 1993-2005. METHODOLOGY: The clinical data and histological and immunohistochemical findings of primary mesenchymal neoplasias were revised using the Department of Pathological Anatomy databases. RESULTS: Six EGISTs were identified. Three were primarily of the omentum and 3 mesenteric. They were found in 4 males and 2 females with an average age of 65.16 years. All were c-KIT positive, and the majority CD34 positive, while 3 were positive for muscle-specific actin. The 3 omentum cases had a mixed spindle/epithelioid pattern and low mitotic rate, while the 3 mesenteric cases had a spindle pattern, with a high mitotic rate in 2 cases, where hepatic metastasis appeared at 6 and 32 months respectively. The 3 omentum cases were alive at the time of writing, and free of disease at 16, 21 and 34 months of follow-up. EGISTs represent 11.9% of GIST cases diagnosed in the hospital over the period 2000-2005. CONCLUSIONS: In this study primary EGISTs of the omentum and mesentery showed clinicopathological and immunohistochemical characteristics similar to those previously in the literature for GISTs of the digestive tract, which supports the hypothesis that these tumors originate from extragastrointestinal c-KIT positive cells. Mesenteric location appears to be associated with a poorer prognosis.

Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma.

OBJECTIVE: The role of molecular and biological factors in ovarian cancer is controversial. We investigated the levels of the estrogen (ER) and progesterone (PR) receptors, HER2/neu, p-53 and Ki 67 in patients with advanced ovarian cancer and correlated the results with the clinical course in order to define their predictive or prognostic significance. METHODS: Paraffin-embedded tumor tissues from 72 patients with ovarian cancer treated from 1999 to 2003 were analyzed. Overexpression of C-erb-B2 was defined as herceptest ++/+++ and positive fluorescence in situ hybridization (FISH) or herceptest +++/+++. Positivity for ER and PR was determined by > or =10% of the cellular membranes immunostained. Statistical analysis was performed to evaluate the prognostic impact of the molecular markers. RESULTS: 49 of the 72 patients were ER + (68%) and 36 PR + (50%). In 45 patients (62.5%) expression of p53 was > or =10%. Overexpression of C-erb-2 was found in 4 tumor samples (5%). A Ki67 labelled nuclear area >30% was found to be associated with a higher rate of complete response (chi(2); p=0.05). None of the biological markers were significantly associated with progression free survival (PFS). By multivariate analysis residual tumor after debulking surgery and ER status were associated with OS (p< or =0.05). CONCLUSIONS: Ki67 nuclear expression >30% is predictive of complete response in advanced ovarian cancer. HER2/neu overexpression is scarce in our study. Positive ER is an independent prognostic factor for OS. Further research with larger studies and hormonal treatment is guaranteed.

Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma

OBJECTIVE: The role of molecular and biological factors in ovarian cancer is controversial. We investigated the levels of the estrogen (ER) and progesterone (PR) receptors, HER2/neu, p-53 and Ki 67 in patients with advanced ovarian cancer and correlated the results with the clinical course in order to define their predictive or prognostic significance. METHODS: Paraffin-embedded tumor tissues from 72 patients with ovarian cancer treated from 1999 to 2003 were analyzed. Overexpression of C-erb-B2 was defined as herceptest ++/+++ and positive fluorescence in situ hybridization (FISH) or herceptest +++/+++. Positivity for ER and PR was determined by > or =10% of the cellular membranes immunostained. Statistical analysis was performed to evaluate the prognostic impact of the molecular markers. RESULTS: 49 of the 72 patients were ER + (68%) and 36 PR + (50%). In 45 patients (62.5%) expression of p53 was > or =10%. Overexpression of C-erb-2 was found in 4 tumor samples (5%). A Ki67 labelled nuclear area >30% was found to be associated with a higher rate of complete response (chi(2); p=0.05). None of the biological markers were significantly associated with progression free survival (PFS). By multivariate analysis residual tumor after debulking surgery and ER status were associated with OS (p< or =0.05). CONCLUSIONS: Ki67 nuclear expression >30% is predictive of complete response in advanced ovarian cancer. HER2/neu overexpression is scarce in our study. Positive ER is an independent prognostic factor for OS. Further research with larger studies and hormonal treatment is guaranteed (AU)

No disponible

Superficial acral fibromyxoma of the toe, with erosion of the distal phalanx. A clinical report.

Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor most often located in the ungual region of the fingers and toes. This tumor was first described in 2001, and since then very few cases have been reported. We present the case of a 35-year-old male with a SAFM located in the toe, with involvement of the nail and erosion of the distal phalanx. The lesion was surgically removed, and the histopathological study confirmed the diagnosis of SAFM. The differential diagnosis must be established with other myxoid tumors and with those lesions showing a predilection for the distal portions of the limbs. After 2 years, the patient remains disease free, with no disability of any kind.

Molecular determinants of Akt-induced keratinocyte transformation.

The PI3K/PTEN/Akt signaling pathway has emerged in recent years as a main player in human cancers, increasing proliferation and decreasing apoptosis of transformed cells, and thus becoming a potential target for therapeutic intervention. Our previous data have demonstrated that Akt-mediated signaling is of a key relevance in the mouse skin carcinogenesis system, one of the best-known models of experimental carcinogenesis. Here, we investigated the involvement of several pathways as mediators of Akt-induced increased proliferation and tumorigenesis in keratinocytes. Tumors produced by subcutaneous injection of Akt-transformed keratinocytes showed increased Foxo3a phosphorylation, but no major alterations in p21(Cip1/WAF1), p27(Kip1) or mdm2 expression and/or localization. In contrast, we found increased expression and nuclear localization of DeltaNp63, beta-catenin and Lef1. Concomitantly, we also found increased expression of c-myc and CycD1, targets of the beta-catenin/Tcf pathway. Such increase is associated with increased phosphorylation and stabilization of c-myc protein as well as increased translation of c-myc and CycD1 due to mTOR activation. Using immunohistochemistry approaches in samples of oral dysplasias and human head and neck squamous cell carcinomas, we confirmed that increased Akt activation significantly correlates with increased DeltaNp63 and CycD expression, c-myc phosphorylation and nuclear accumulation of beta-catenin. Collectively, these results demonstrate that Akt is able to transform keratinocytes by specific mechanisms involving transcriptional and post-transcriptional processes.

beta-Catenin, Nf-kappaB and FAS protein expression are independent events in head and neck cancer: study of their association with clinical parameters.

In spite of much effort, no good markers have yet been found for predicting prognosis or response to therapy in advanced head and neck squamous cell carcinoma (HNSCCs) patients. beta-catenin, a protein involved in the cytoskeleton, cell-cell adhesion and gene transcription, is a factor associated with tumour progression. Recently, an interaction has been reported between beta-catenin, and NF-kappaB coupled with an inverse association of beta-catenin, and FAS (CD95/APO-1) protein expression in breast and colorectal tumours. To confirm these observations and to test their clinical impact in HNSCCs we have evaluated the expression of beta-catenin, NF-kappaB and FAS proteins. We used tissue microarrays to simultaneously analyse the levels of these proteins immunohistochemically in 118 HNSCCs. Among the 113 tumours evaluable for beta-catenin, increased and decreased levels were detected in 41 (36%) and 62 (55%) of the tumours, respectively. beta-catenin, protein staining was mainly membranous but 10 tumours (9%) showed the clear presence of protein in the cytoplasm, and none in the nucleus. Moreover, 81% of the tumours had decreased FAS protein expression, indicating that loss of FAS protein is a common feature of HNSCCs. Abnormal or nuclear NF-kappaB staining was observed in 24% of the tumours. No association was detected between the expression levels of the proteins evaluated. Regarding clinical associations, tumours from the hypopharynx had significantly lower levels of beta-catenin expression than those from other locations (P<0.05). Moreover, our data revealed that patients whose tumours had low levels of beta-catenin protein expression had decreased survival probability (24.8 months vs. NR, P=0.03) and reduced response to therapy (15.4 vs. 43 months; P=0.01) compared with patients whose tumours had high levels of beta-catenin. Taken together, our observations indicate that beta-catenin, NF-kappaB and FAS expression are independent events during HNSCC development and that levels of beta-catenin protein may identify subsets of advanced HNSCCs patients with different prognosis and response to therapy capabilities.

[Pleural mesothelioma: experience with 62 cases in 9 years]. / Mesotelioma pleural: experiencia durante 9 años y descripción de 62 casos.

OBJECTIVES: To describe the diagnostic approach, clinical and radiological characteristics, and survival of patients with pleural mesothelioma treated in our hospital over a 9-year period. PATIENTS AND METHOD: All patients with a diagnosis of pleural mesothelioma diagnosed in our hospital from January 1992 through December 2000 were studied. RESULTS: Sixty-two patients (49 men) with a mean age of 65 years (range, 45-85) were diagnosed. Probable or known contact with asbestos was established for 41 patients (66%). Ninety-four percent of the patients had chest pain or dyspnea at the onset of clinical assessment. The tumor was situated in the right hemithorax in 33 patients; 59 patients had pleural effusion, and 3 only had pleural thickening. The pleural fluid was bloody in 19% of patients, glucose levels were less than 60 mg/dL in 44%, and the pH of pleural fluid was less than 7.20 in 19%. The diagnosis was established by pleural biopsy for 52%, and by thoracoscopy or thoracotomy for 44%. The median survival was 11 months (95% confidence interval, 8-15); the probability of survival was 0.22 after 2 years, and 0.09 after 5. For the subgroup of patients with epithelial tumors the probability of survival was 0.31 after 2 years and 0.16 after 5 years. In the univariate analysis the predictors of survival were general clinical status (Karnofsky scale), platelet count, serum albumin level, pleural pH, glucose and lactate dehydrogenase levels, and histological type. CONCLUSIONS: The clinical, radiological, and biochemical characteristics of the pleural fluid from patients with pleural mesothelioma and their survival rate were described.

Mesotelioma pleural: experiencia durante 9 años y descripción de 62 casos / Pleural mesothelioma: experience with 62 cases in 9 years

OBJETIVO: Describir las características clínicas, radiológicas, el método diagnóstico y la evolución de los pacientes con mesotelioma pleural estudiados en nuestro hospital durante 9 años. PACIENTES Y MÉTODO: Se ha incluido a todos los pacientes diagnosticados de mesotelioma pleural en nuestro hospital entre enero de 1992 y diciembre de 2000. RESULTADOS: Se ha incluido a 62 pacientes (49 varones), con una edad media de 65 años (rango: 45-85). De ellos, 41 (66 por ciento) tenían antecedentes de contacto con asbesto seguro o probable. El 94 por ciento presentaba dolor torácico o disnea al comenzar el estudio; el tumor era derecho en 33 pacientes, en 59 había derrame pleural y en 3 sólo engrosamiento pleural.El líquido pleural era hemático en el 19 por ciento de los pacientes. El 44 por ciento tenía concentraciones de glucosa inferiores a 60 mg/dl, y en el 19 por ciento el pH pleural era inferior a 7,20. El diagnóstico se realizó en el 52 por ciento de los pacientes mediante biopsia pleural, y en el 44 por ciento mediante toracoscopia o toracotomía. La mediana de supervivencia fue de 11 meses (intervalo de confianza del 95 por ciento, 8-15); la probabilidad de supervivencia fue de 0,22 a los 2 años, y del 0,09 a los 5 años. Para los tumores epiteliales la probabilidad de supervivencia era de 0,31 a los 2 años y de 0,16 a los 5 años. En el análisis univariante se asociaron al pronóstico de supervivencia el estado clínico general (escala de Karnofsky), el número de plaquetas, la albúmina sérica, así como el pH, la glucosa y la lactatodeshidrogenasa pleurales y el tipo histológico. CONCLUSIONES: Se describen las características clínicas, radiológicas, del líquido pleural y la supervivencia de los pacientes con mesotelioma pleural (AU)

Paget's disease of the glans penis secondary to transitional cell carcinoma of the bladder: a report of two cases and review of the literature.

BACKGROUND: Extramammary Paget's disease of the glans penis secondary to transitional cell carcinoma (TCC) of the bladder is rare, with only a few cases reported in the literature. We report two new cases, one detected before diagnosing bladder TCC. METHODS: We describe the clinicopathologic features of two patients with intraepithelial spread of glans TCC and the histochemical and immunohistochemical features of the neoplasm. RESULTS: Light microscopy detected intraepithelial proliferation of neoplastic, large, pale cells located predominantly in the basal and parabasal layers of the epithelium. The pagetoid cells showed positive cytoplasmic staining for mucosubstances and immunoreactivity for CK20. The previously reported cases are reviewed and the differential diagnosis is discussed. CONCLUSIONS: As many benign and malignant glans lesions may be clinically similar, histologic study is necessary to correctly diagnose primary lesions and promptly detect underlying asymptomatic visceral malignancies initially presenting as Paget's disease.

Autoimmune enteropathy in an adult with autoimmune multisystemic involvement.

We describe the case of a 58-year-old woman with autoimmune enteropathy associated with thyroiditis, gastritis, transitory neutropenia, sicca syndrome and severe axonal polyneuropathy of autoimmune origin. Enterocyte autoantibodies were not detected. However, predisposition to autoimmune disease was indicated by the presence of high titres of anti-gastric parietal cell, anti-thyroglobulin, anti-thyroid peroxidase and anti-neutrophil antibodies. CD4+ and CD8+ lymphocytes were equally distributed in the lamina propria of the small intestine, but CD8+ cells were highly represented among intraepithelial lymphocytes.

Primary cutaneous adenosquamous carcinoma: a case report and review of the literature.

BACKGROUND: Adenosquamous carcinoma (ASC) of skin is a rare but distinctive neoplasm that usually exhibits an aggressive course. To date, 13 well-documented and undisputed cases of primary cutaneous ASC have been reported. This term has been used for tumors with better prognosis, such as mucoepidermoid carcinomas and acantolytic squamous cell carcinomas, originating confusion. We report a primary cutaneous ASC and review the literature. METHODS: In this report a woman with primary ASC of the skin was studied. Histopathological examination and immunohistochemical stains were performed. RESULTS: The tumor had two components: conventional squamous cell carcinoma merging with adenocarcinoma. After a local recurrence and lymph node metastases, the patient has no evidence of disease 8 months later. CONCLUSIONS: Pathologists should reserve the term ASC for tumors exhibiting the above mentioned appearance. In such circumstances, a metastatic origin must always be excluded.

Prognostic value of cytosolic p53 protein in breast cancer.

The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by immunoblotting using the monoclonal antibody PAb 1801. Two hundred and five carcinomas (45%) showed positive p53 accumulation and 55% were p53 negative. When comparing p53 positivity and other clinicopathological parameters, significant differences were found with younger age (p = 0.017), premenopausal status (p = 0.003), increasing tumor size (p = 0.026), negative estrogen receptor (p = 0.003) and negative progesterone receptor (p = 0.047), but not with histologic grade, axillary lymph node status, stage or erbB-2 expression. With a median follow-up of 34 months (range 3-70), relapse has occurred in 73 patients. Disease-free survival curves showed that patients with p53-positive tumors had a significantly shorter disease-free survival than patients with p53-negative carcinomas (log-rank test, p = 0.027). A multivariate analysis of disease-free survival showed that p53, tumor size, histologic grade and progesterone receptor had significant independent prognostic value. The immunoblotting technique was controlled with p53 immunohistochemistry in 94 paired samples. We obtained a statistically significant correlation (p = 0.0004) between the two methods. Our results show that the immunoblotting technique offers an alternative approach in evaluating the p53 status of breast biopsy material using cytosolic extracts, and confirm that p53 accumulation is a significant independent indicator of a poor prognosis in operable breast carcinoma.

Fine needle aspiration of breast myofibroblastoma. A case report.

BACKGROUND: The use of fine needle aspiration cytology (FNAC) for the diagnosis of breast diseases in men has received little attention. We report the cytologic and histologic findings of myofibroblastoma of the breast in a 52-year-old man. CASE: Smears disclosed irregular and cohesive sheets of cells, with ill-defined cytoplasm and oval nuclei containing single nucleoli. The nuclear membrane was frequently grooved, and occasional intranuclear cytoplasmic inclusions (pseudoinclusions) were also found. The background was clean and contained scarce collagenous stroma and fragments of myxoid material. To the best of our knowledge, there have been only seven previous reports of breast myofibroblastoma in which the cytologic features are well documented, and none of them mention the presence of pseudoinclusions. CONCLUSION: FNAC could suggest the diagnosis of this distinctly uncommon tumor if evaluated together with the clinical and radiologic findings.

Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura.

AIMS: To determine the value of immunohistochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy we optimized a double panel of MOC-31 and HBME-1 and compared the results with others from the literature. METHODS AND RESULTS: A multi-antibody panel was applied to biopsy samples from 44 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura. We used monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), LeuM1, vimentin, desmin, epithelial related antigen (MOC-31) and mesothelial cell (HBME-1). Positivity for MOC-31 and Ber-EP4 was found to have the highest nosologic sensitivity (94.1% and 84.6%, respectively) and specificity (86.3% both antibodies) for carcinoma. Positive staining for HBME-1 and vimentin had the highest sensitivity (90.9% and 100%, respectively) and specificity (91.3% and 60%, respectively) for mesothelioma. A two-marker antibody panel with HBME-1 and MOC-31 was the most efficient for the distinction between carcinoma and malignant pleural mesothelioma. CONCLUSION: A combination of MOC-31 (an anti- epithelial marker) and HBME-1 (an anti-mesothelial marker) has a diagnostic efficiency of 76.1% for the distinction between carcinoma and mesothelioma in pleura.