Paulette Mhawech

Downregulation of 14-3-3 sigma in ovary, prostate and endometrial carcinomas is associated with CpG island methylation

The 14-3-3σ inhibitor of cell cycle progression has been shown to be target of epigenetic deregulation in many forms of human cancers; however, its role in urological and gynecological cancers has not been studied. Here, we have analyzed the expression of 14-3-3σ, wild-type p53 and mutated p53 in over 300 cases of the most common cancers occurring in the urological and gynecological tracts and its normal counterpart tissue by immunohistochemistry using the multiple tumor tissue microarrays. 14-3-3σ expression was detected in normal epithelia from most organs with sporadic expression in renal tubules and absence in the testis. In contrast to normal tissue, 14-3-3σ expression was lost in 40–60% of adenocarcinomas of the breast, ovary, endometrium and prostate. There was no association between 14-3-3σ and wild-type/mutated p53 expression. By performing methylation-specific PCR, we showed a close association of 14-3-3σ CpG island methylation and low protein expression levels of 14-3-3σ. In addition, a direct link of 14-3-3σ mRNA expression levels to CpG island methylation is demonstrated in two human cancer cell lines. Loss of 14-3-3σ expression due to promoter hypermethylation may represent the most frequent molecular aberration in ovarian, endometrial and prostate adenocarcinomas.

Inherited Giant Platelet Disorders Classification and Literature Review

Inherited giant platelet disorders are extremely rare. The aim of this article is to review the clinical and laboratory features of this heterogeneous group and to arrive at a working classification. We conducted our literature search using the National Library of Medicine database. A total of 12 clinical entities were described. We classified them into 4 groups depending on the clinical and structural abnormalities. The pathophysiology of these disorders is largely unknown, and more research is needed, particularly in the light of recent advances in laboratory medicine. This review may provide a valuable reference for clinicians and may form a basis for future classification and research.

Myelodysplastic syndrome: review of the cytogenetic and molecular data.

Myelodysplastic syndrome (MDS) is a monoclonal disorder of the pluripotent stem cell that frequently evolves into acute leukemia. MDS is characterized by trilineage dysplasia and by ineffective hematopoiesis. The etiology of MDS is poorly understood. However, the frequent association of chromosomal abnormalities (deletions, inversions, translocations, trisomies and monosomies) with MDS suggests that an oncogene, or a tumor suppressor gene might be involved in the pathogenesis and evolution of this disorder. This review summarizes the clinical, laboratory, chromosomal and prognostic findings of some of the cytogenetic abnormalities such as; 20q deletion, chromosome 5, 7 and 3 abnormalities, 17p-syndrome, trisomy 8, and loss of Y chromosome. In addition, this review goes into the discussion of the most recent development in the field of molecular biology to understand some of the mechanisms resulting in the development and progression of MDS.

Immunohistochemical expression of 14-3-3 sigma protein in human urological and gynecological tumors using a multi-tumor microarray analysis

14‐3‐3 σ is an exclusive epithelial marker and data on its expression in different malignancies are very scarce. The aims of the present study are to screen its expression in the most common neoplasms occurring in the urological and gynecological tract and to evaluate its use as a diagnostic marker. A tissue microarray was constructed using 350 samples from 13 different neoplasms. Immunohistochemical analysis using a polyclonal 14‐3‐3 σ antibody was performed. Overall, this protein was positive in 141 and negative in 209 tumors. The most frequent expression was seen in squamous cell carcinoma of the cervix and urothelial bladder carcinoma, followed by prostatic and endometrial adenocarcinoma. 14‐3‐3 σ was able to distinguish prostate adenocarcinoma from urothelial bladder carcinoma, with an odds ratio of 0.028 (P = 0.001; 95% CI, 0.0003–0.222), and distinguish seminoma from embryonal carcinoma of the testis, with an odds ratio of 0.061 (P = 0.009; 95% CI, 0.007–0.5014). It also has a good value in differentiating renal clear cell carcinoma from papillary carcinoma, with an odds ratio 0.470 (P < 0.001; 95% CI, 0.008–0.261). 14‐3‐3 σ seems to have good potential use as an epithelial marker, after confirmation with further targeted studies. Finally, as with all immunohistochemical markers, we can optimize the utility of this protein to distinguish tumor mimics by including it in an appropriate immunohistochemical panel.

Value of immunohistochemistry in staging T1 urothelial bladder carcinoma

PURPOSE The subclassification of T1 bladder tumors into T1A and T1B has an important prognostic significance and a great impact on patient management. Unfortunately, staging T1 tumors is highly subject to interpathologist variation that can be critical for patients included in randomized clinical trials. To determine the value of immunohistochemistry (IHC), such as desmin and keratin, in comparison to hematoxylin-eosin (H&E) in classifying T1 stage disease, we retrospectively examined 93 consecutive cases diagnosed at our department. MATERIALS AND METHODS The study was conducted in two phases (H&E then IHC), each in two time periods. First H&E, and then IHC slides were reviewed independently by two experienced pathologists and discrepant cases from each phase were discussed between the two pathologists to reach a final decision. RESULTS The two methodologies (H&E and IHC) showed total agreement in 76 out of 93 cases. IHC downstaged seven cases, that is from T1B to T1A, upstaged four cases, that is from T1A to T1B, lowered the rate of imprecision and eliminated the disagreement between the two pathologists. However, IHC failed to subclassify T1 tumors in three cases. Finally, the discussion supported by the IHC was very useful in reaching the diagnosis in some cases. CONCLUSIONS IHC appears to be a useful tool in staging T1 bladder cancer, especially in difficult cases where specimen orientation and artifact could create a major hindrance in reaching an accurate diagnosis.

Human achaete-scute homologue (hASH1) mRNA level as a diagnostic marker to distinguish esthesioneuroblastoma from poorly differentiated tumors arising in the sinonasal tract.

Distinction of high-grade esthesioneuroblastomas from other poorly differentiated tumors arising in the nasal cavity is an important diagnostic challenge because it determines patient management and prognosis. The human achaete-scute homologue (hASH1) gene is critical in olfactory neuronal differentiation and is expressed in immature olfactory cells; therefore, it could have potential use as a diagnostic marker The aim of the present study was to determine the value of hASH1 messenger RNA (mRNA) levels in differentiating esthesioneuroblastoma from other poorly differentiated tumors. A real-time polymerase chain reaction assay was developed, permitting the comparative determination of hASH1 mRNA levels in triplicate in a double-blind pilot study including 24 frozen cases of esthesioneuroblastoma and poorly differentiated tumors. All 4 positive cases were esthesioneuroblastomas, and all 19 poorly differentiated tumors were negative. In addition, there was an inverse association between the grade of esthesioneuroblastomas and hASH1 mRNA levels. The hASH1 mRNA level might represent a useful tool for distinguishing esthesioneuroblastoma from poorly differentiated tumors of the sinonasal region.

Motility-related protein-1 (MRP-1/CD9) expression can predict disease-free survival in patients with squamous cell carcinoma of the head and neck

CD9 is a transmembrane protein that has been implicated in cell adhesion, motility and proliferation, and numerous studies have demonstrated the prognostic value of its expression in different solid tumours. The purpose of this study is to determine the predictive value of CD9 in squamous cell carcinoma (SCC) of the head and neck. A total of 153 cases were examined for CD9 expression using immunohistochemistry applied on formalin-fixed, paraffin-embedded tissue. Cases were stratified in two categories depending on CD9 expression, as positive (⩾50% positive cells) or reduced (<50%). In all, 108 cases were positive for CD9 (85 cases with membranous, and 23 with both membranous and cytoplasmic staining) and 45 reduced expression. Reduced CD9 expression was significantly associated with high grade (P=0.0007) and lower disease-free survival (DFS) (P=0.017). The latter retained its significance in the multivariate analysis. When the 23 cases with both membranous and cytoplasmic patterns were studied as a separate subgroup, there were significant associations between CD9 expression and tumour grade (P=0.025) (95% CI 11–68), tumour stage (P=0.08) (95% CI 3.5–86) and the occurrence of any failure (P=0.083) (95% CI −1.7–57). Immunohistochemical CD9 expression proved to be an independent prognostic factor in SCC of the head and neck, and it may detect patients at a high risk of recurrence. In addition, the cytoplasmic pattern seems to have an even more significant value. However, this finding is limited to the small number of cases with this pattern.

Mucoepidermoid carcinoma of Stensen's duct: a case report and review of the literature.

Mucoepidermoid carcinoma of Stensens duct is a rare neoplasm, with only five cases reported in the literature.