Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours.

BACKGROUND: Microsatellite instability (MSI) is a molecular phenotype due to defective DNA mismatch repair (MMR) system. It is used to predict outcome of colorectal tumours and to screen tumours for Lynch syndrome (LS). A pentaplex panel composed of five mononucleotide markers has been largely recommended for determination of the MSI status. However, its sensitivity may be taken in default in occasional situations. The aim of the study was to optimise this panel for the detection of MSI. METHODS: We developed an assay allowing co-amplification of six mononucleotide repeat markers (BAT25, BAT26, BAT40, NR21, NR22, NR27) and one polymorphic dinucleotide marker (D3S1260) in a single reaction. Performances of the new panel were evaluated on a cohort of patients suspected of LS. RESULTS: We demonstrate that our assay is technically as easy to use as the pentaplex assay. The hexaplex panel shows similar performances for the identification of colorectal and non-MSH6-deficient tumours. On the other hand, the hexaplex panel has higher sensitivity for the identification of MSH6-deficient tumours (94.7% vs 84.2%) and MMR-deficient tumours other than colorectal cancer (92.9% vs 85.7%). CONCLUSION: The hexaplex panel could thus be an attractive alternative to the pentaplex panel for the identification of patients with LS.

Clinical impact of MUC1 and MUC4 expression in Barrett-associated oesophageal adenocarcinoma.

AIMS: To study the expression of MUC1 and MUC4 mucins in Barrett-associated oesophageal adenocarcinoma and coexisting lesions of the carcinogenic sequence (normal mucosa, metaplasia, dysplasia) if present, and to investigate their prognostic significance. METHODS: The expression profiles of MUC1 and MUC4 were investigated by immunohistochemistry in tissue samples obtained from consecutive patients with primary surgically resected lower third oesophageal adenocarcinoma (OA) between 1997 and 2002. Histopathological parameters, recurrence and long-term survival were correlated with the number of cells stained. RESULTS: All 52 patients exhibited OA, with 25 patients (48.1%) having associated Barrett oesophagus lesions (metaplasia or/and dysplasia). MUC1 and MUC4 were expressed in 52 and 41 of the 52 patients with adenocarcinoma (100% and 78%), respectively. All samples expressed MUC1 strongly. The prevalence of MUC4 staining was significantly decreased in metaplasia compared with normal mucosa (53% versus 92%, p<0.001). No correlation was found between the level of MUC1 or MUC4 expression in OA and histopathological variables, recurrence or survival. CONCLUSIONS: MUC1 and MUC4 are strongly expressed in OA. The results do not support a role for these two membrane-bound mucins as either a phenotypic or a prognostic marker for the development of Barrett OA. There are several other membrane-bound mucins that have not yet been evaluated in this situation.

[Localized amyloidosis of the cavum]. / Amylose localisée du cavum.

INTRODUCTION: Amyloidosis is characterized by extracellular deposits of proteins. OBSERVATION: A 66 year-old patient presented with a pseudo-tumoral amyloidosis of the cavum. Clinical and biological examinations confirmed the localized aspect of the disease and immunohistochemical exploration identified a type AL amyloidosis. COMMENTS: The disease may be diffuse involving many organs and leading to various clinical manifestations. It can also be localized and take on a pseudo-tumoral aspect. Localised amyloidosis is a rare lesion of the upper aero-digestive tract, predominating in the larynx. Nasopharyngeal involvement is exceptional.

Immunohistochemical detection of Fas and Fas ligand in sarcomatoid renal cell carcinoma.

Sarcomatoid renal cell carcinomas (SRC) are rare neoplasms associated with a very poor prognosis. The aim of this study was to evaluate biomarker expression and clinical significance in this uncommon renal cancer. Cytokeratin, epithelial membrane antigen, vimentin, desmin, smooth muscle actin, CD34, S-100 protein, MIB 1, p53, Fas and Fas ligand immunohistochemical expression was investigated in seven renal cell carcinomas with sarcomatoid changes. No significant difference between sarcomatoid and nonsarcomatoid areas was observed with the different biomarkers, excepted for Fas ligand. Fas expression was diffuse in sarcomatoid and nonsarcomatoid areas. However, Fas ligand had a higher expression in sarcomatoid in comparison to nonsarcomatoid areas. Our results showed that Fas and Fas ligand are both expressed in renal cancer. We suggest that the aggressive behavior of sarcomatoid carcinoma may be related to a higher expression of Fas ligand by tumor sarcomatoid cells. These findings may indicate that Fas ligand is a possible therapeutic molecular target for treatment of SRC.

Mucin gene transcripts in benign and borderline mucinous tumours of the ovary: an in situ hybridization study.

Mucinous tumours of the ovary are characterized by mucin-secreting cells exhibiting a variable endocervical, intestinal, gastric or pancreatobiliary phenotype as ascertained by microscopy, electron microscopy, histochemistry or immunohistochemistry. The molecular mechanisms underlying the tumourigenesis process are not well understood. The mucin glycoproteins expressed by ovarian mucinous tumours have not been fully characterized, but mucins are known to be implicated in tumour progression in various epithelial neoplasms. The purpose of this study was to evaluate the expression of mucin genes (MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6) in ovarian mucinous tumour cells, to relate MUC gene expression to the histological diagnosis, and to compare the expression patterns with those observed in normal tissues. The expression of mucin genes was evaluated by in situ hybridization in 21 mucinous tumours (11 adenomas and ten borderline tumours). Heterogeneity of expression correlated with morphological heterogeneity. Intense expression of the MUC5AC gene, suggesting a gastric surface cell phenotype, was demonstrated in 18/21 tumours (86%). Goblet cells expressing the MUC2 gene and columnar cells expressing the MUC3 gene were consistent with an intestinal phenotype, which was observed in 15 tumours (71%) including nine adenomas and six borderline tumours. Major expression of MUC4 and MUC5B consistent with an endocervical phenotype was observed in seven benign (64%) and three borderline (30%) tumours. In all, the MUC profiles suggested gastrointestinal-type cells in 13 cases (62%), gastric-type cells in five cases (24%), and intestinal-type cells in two cases (one benign, one borderline) (9%); the results were inconclusive in one borderline tumour (5%). It is concluded that gastric and, to a lesser degree, intestinal differentiation are early and almost constant events in ovarian mucinous tumourigenesis.

Why do frozen sections have limited value in encapsulated or minimally invasive follicular carcinoma of the thyroid?

The diagnosis of encapsulated or minimally invasive follicular carcinoma of the thyroid requires the proof of vascular or capsular invasion. The aim of the present study was to evaluate the relationship between intraoperative diagnosis (benign, suggestive of carcinoma, or malignant) and the final histopathologic criteria for encapsulated or minimally invasive follicular carcinoma (tumor size, capsular invasion, vascular invasion, and differentiation). This was a retrospective study of 63 cases of encapsulated or minimally invasive carcinomas, with the final histopathologic diagnosis taken as the "gold standard." The sensitivity of frozen sections for the diagnosis of malignant neoplasm was 17%. The median number of vascular invasions was 1, identified with a mean number of 9 paraffin-blocks of the tumor. In most cases, intraoperative frozen sections are unable to establish the proof of malignant neoplasm. Intraoperative study of tumor differentiation is useful to select follicular tumors that require a rapid definitive diagnosis and a completion thyroidectomy within 48 to 72 hours (73% of the cases in our study).

[Leiomyosarcoma and stromal tumor of the pancreas]. / Léiomyosarcome et tumeur stromale du pancréas.

A tumor of the head of pancreas was an incidental finding on US of two patients aged 52 and 61 years presenting with abdominal pain. The tumor was studied by computed tomography, MRI and endoscopic ultrasonography. Surgical biopsy of a liver lesion was performed in one case and partial duodenopancreatectomy was performed in the other case. Histological evaluation, including immunohistochemistry, showed leiomyosarcoma and stromal tumor respectively. Whatever the site of origin, most mesenchymal pancreatic tumors are hypervascular, heterogeneous and have a necrotic center.

Inflammatory pseudotumor of the renal pelvis. A report of 2 cases with clinicopathologic and immunohistochemical study.

We describe 2 cases of inflammatory pseudotumor of the renal pelvis. Case 1, the male patient, was 37 years old, and case 2, the female patient, was 54 years old. Both patients presented with macroscopic hematuria and flank pain. Computed tomographic (CT) scan and ureterocystoscopy revealed in case 1 a mass in the left renal pelvis and the calyces. In case 2, urography showed a lacuna of the renal pelvis, and CT scan showed an irregular thickening of the renal pelvis. In both cases, the preoperative clinical diagnosis was urothelial carcinoma, and both patients underwent nephrectomy. Microscopic examination revealed in case 1 a tumor of the renal pelvis composed of spindle cells with eosinophilic cytoplasm in a myxoid and vascular stroma with abundant inflammatory infiltrate. In case 2, the tumor was composed of densely basophilic spindle cells in a fascicular pattern intermingled with lymphocytes and plasma cells and involving the lamina propria of the renal pelvis. The spindle cells reacted strongly with antibody to vimentin and focally with antibodies to smooth muscle actin and muscle-specific actin. In the urogenital tract inflammatory pseudotumor involves preferentially the urinary bladder. Rare cases have been reported in the kidney. The 2 cases presented here are unusual due to the location in the renal pelvis, mimicking urothelial carcinoma.

Solitary fibrous tumour of the kidney.

Solitary fibrous tumours are relatively rare neoplasms initially described in the pleura. Such lesions are now reported in many extrathoracic sites. To our knowledge, only 8 cases have been reported in the kidney. All these cases were benign. We report a patient with a solitary fibrous tumour of the kidney with infiltration of the wall of the renal vein. Microscopic examination showed proliferation of spindle cells with a prominent vascular haemangiopericytoma-like pattern. Hypercellular areas were admixed with hyalinized collagenous zones. The neoplastic cells stained for vimentin and CD34. CD31 was negative. Biologically, we did not find any arguments for malignancy: the flow cytometric study showed diploid histograms, and immunostaining for p53 was negative.

[Ovarian mucinous tumor of gastric and intestinal type associated with Peutz-Jeghers syndrome: in situ hybridization study of apomucin gene transcripts]. / Tumeur mucineuse ovarienne de type gastrique et intestinal associée au syndrome de Peutz-Jeghers; étude en hybridation in situ des transcrits des gènes d'apomucines.

Occurrence of mucinous tumors is favored by Peutz-Jeghers syndrome (PJS). A case of bilateral ovarian mucinous tumor associated with ovarian mature teratoma occurring in a 22-year-old woman with PJS was reported. Tumor cells included 5 cell types: tall columnar mucinous pale cells with neutral mucins; goblet cells with acidic nonsulfated mucins; non mucinous columnar cells; mucinous cuboidal cells lining small glands; endocrine cells. Expression of the MUC2, MUC3, MUC5AC and MUC6 genes was demonstrated by in situ hybridization according to cell type. Some atypia and numerous mitotic figures were observed in basal glands. Diagnosis was ovarian borderline mucinous tumor with gastric and intestinal phenotype associated with PJS.