p53 and c-jun expression in urinary bladder transitional cell carcinoma: correlation with proliferating cell nuclear antigen (PCNA) histological grade and clinical stage.

OBJECTIVE: To investigate p53 and c-jun oncoproteins and proliferating cell nuclear antigen (PCNA) in transitional cell urinary bladder carcinomas (TCCs) and to determine their relationships to tumour grade, stage and survival. MATERIALS AND METHODS: The expression of p53, c-jun and PCNA was studied using immunohistochemistry in formalin-fixed, paraffin-embedded tissues in a series of 110 TCCs. RESULTS: 58% of our cases were positive for p53 and 88% for c-jun. A statistically very significant correlation (p < 0.0001) was observed between p53 and c-jun (r = 0.781), p53 and PCNA (r = 0.772), c-jun and PCNA (r = 0.831) as well as between each of the two oncoproteins and the histological grade and clinical stage (p < 0.001). There was no correlation of either p53, PCNA or c-jun with clinical outcome in terms of patients survival. CONCLUSION: p53 and c-jun proteins' overexpression are strongly related to rapid tumour cell proliferation and hence with aggressive growth in urinary bladder TCC. PCNA score remains an important prognostic index in transitional cell carcinoma of the bladder.

MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor.

p53 and the murine double minute 2 (MDM2) oncoprotein expression was evaluated in paraffin-embedded tissue from 61 patients with central nervous system gliomas (53 astrocytomas and eight oligodendrogliomas) and related to proliferation-associated markers [i.e. proliferating cell nuclear antigen (PCNA), Ki-67 and nuclear organizer regions (NORs)] and epidermal growth factor receptor (EGFR). We used the monoclonal antibodies PC-10, MIB-1, DO-1, 1B1O and EGFR 113 and the colloid silver nitrate (AgNOR) technique. MDM2 and p53 were co-expressed in 28% of cases. A p53-positive/MDM2-negative phenotype was observed in 15% and a p53-negative/MDM2-positive phenotype in 20% of cases. There was a positive correlation of p53 and MDM2 expression with grade and proliferation indices. Univariate analysis in the group of diffuse astrocytomas showed that older age, high histological grade, high PCNA labelling index (LI) and high AgNOR score were associated with reduced overall survival (P < 0.05). p53 LI, Ki-67 LI, AgNOR score, tumour location and grade influenced disease-free survival (P < 0.05), whereas the only parameters affecting post-relapse survival were histological grade and Ki-67 LI (P < 0.1). Multivariate analysis revealed that age, radiotherapy, PCNA LI and p53 LI were the independent predictors of overall survival. p53 LI, Ki-67 LI, MDM2 LI, EGFR LI, grade and type of therapy were independent predictors of disease-free survival, and grade was the only independent predictor of post-relapse survival. Our results indicate that p53 LI and MDM2 LI, EGFR expression as well as proliferation markers (PCNA and Ki-67) are useful indicators of overall and disease-free survival in diffuse astrocytoma patients.

The role of p53, MDM2 and c-erb B-2 oncoproteins, epidermal growth factor receptor and proliferation markers in the prognosis of urinary bladder cancer.

The immunohistological expression of p53 and MDM2 oncoproteins was examined in paraffin embedded tissue from 106 patients with transitional cell carcinoma of the urinary bladder and was related to various clinicopathological features, the expression of proliferation associated markers (proliferating cell nuclear antigen - PCNA - and Ki-67), c-erb B-2 oncoprotein and epidermal growth factor receptor (EGFR), as well as to survival. MDM2 immunoreactivity was seen in 38% of our cases, and in 14% was accompanied by p53 positive immunohistochemistry. The rate of p53 positivity was associated with grade, stage and papillary status, whereas MDM2 immunopositivity increased with grade and stage (Ta VS T1), and MDM2 labeling index (LI) with stage. MDM2 expression was related to p53 expression and less strongly to proliferation rate (Ki-67 LI). The simultaneous p53 and MDM2 expression was more frequently observed in higher grade and stage tumours. C-erb B-2, EGFR and proliferation marker expression increased with grade, stage and non-papillary configuration. In univariate analysis high grade, solid growth pattern, advanced T-category, cystectomy, EGFR and Ki-67 expression were linked to shorter overall survival but only Ki-67 LI, along with T-category and type of therapy, had independent prognostic value. C-erb B-2 expression and stage were the two independent predictors of disease-free survival and Ki-67 LI and EGFR LI the independent predictors of post-relapse survival. For patients with superficial tumors PCNA LI emerged as the single independent determinator of survival. p53 and MDM2 expression did not appear to have any significant impact on survival, although the simultaneous expression of p53 and MDM2 turned out to be a highly significant parameter of shortened overall survival in univariate analysis.

p53 expression in hepatocellular carcinoma in Greece. Correlation with epidemiological and histopathological data.

Localization of p53 oncoprotein was investigated in 60 hepatocellular carcinomas (HCCs) from patients resident in the Northwest and Central Greece. The streptavidin-biotin complex immunoperoxidase method was performed in archival formalin-fixed, paraffin-embedded material, using the monoclonal antibody DO-1. The aim of our study was to correlate p53 expression with histological and epidemiological data. p53 overexpression in patients with serological hepatitis B or C was greater (47%) as compared to that observed in patients without these markers (p < 0.01). Morphologically normal liver tissue (NLT) and liver cell dysplasia (LCD) was recognized adjacent to HCC developing on non-alcoholic cirrhotic livers in patients with "NonA, NonB hepatitis" from between 1975-1986. NLT and LCD and p53 oncoprotein was expressed in 10% of the cases. No relationship was observed between p53 expression and tumor histological grade, patients' age and sex. These results suggest that in Northwest and Central Greece, p53 oncosupressor gene may be involved in some HCCs; it may be associated with viral chronic infection disease (HBV or HCV), and as yet with uncharacterized viruses which remain to be determined.

Topographical immunohistochemical expression of bcl-2 protein in human liver lesions.

Immunolocalization of the bcl-2 protein was investigated in 60 hepatocellular carcinomas, 10 cholangiocarcinomas. 15 metastatic adenocarcinomas as well as in 37 non-neoplastic liver lesions. The three-step immunoperoxidase method was performed in archival, routinely processed material. bcl-2 protein was not identified either in neoplastic, dysplastic or normal hepatocytes, whereas it was observed in bile ductules and small bile duct epithelia, but not in the epithelium lining large bile ducts. All cases of cholangiocarcinoma and 60% of metastatic adenocarcinomas were bcl-2 positive. bcl-2 appears to be an additional marker in distinguishing hepatocellular carcinoma from cholangiocarcinoma or metastatic adenocarcinoma. Also, bcl-2 does not seem to be involved in human liver hepatocyte survival.

Hepatobiliary cystadenoma with mesenchymal stroma (CMS) in association with unilateral mucinous cystadenoma of the ovary (MCO): case report and review of the literature.

The case of a patient with a cystadenoma with mesenchymal stroma (CMS) of the liver in association with asymptomatic unilateral mucinous cystadenoma of the right ovary (MCO) is reported. Immunohistochemical analysis of both lesions showed an identical profile. CA19-9 was expressed in the epithelial lining of both, intrahepatic CMS and MCO, without a parallel serum elevation. A probable common pathway of synchronous histogenesis for these lesions is hypothesised. The etiology of CMS remains obscure suggesting a multifactorial process implicating sex-related (hormone-dependent?) synergic and environmental factors, which probably act in different stages of organogenesis. Partial hepatectomy and right salpingo-oophorectomy were performed. Four years after surgery, the patient remains well with no evidence of residual or recurrent disease.

Enteric type villoglandular papillary adenocarcinoma of the uterine cervix associated with in situ squamous cell carcinoma. Case report and review of the literature.

A very rare case of enteric-type villoglandular papillary adenocarcinoma of the uterine cervix associated with in situ squamous cell carcinoma in a 21-year-old nulliparous caucasian woman is reported. Adjacent to the infiltrative component of an enteric-type lesion, cervical intraepithelial glandular neoplasia (CIGN) was also noticed. Histochemical detection of acetylated sialomucins demonstrates the enteric-type nature of this neoplastic (via metaplasia) process. The patient was treated by conization. Follow-up was uneventful one year after diagnosis.

Expression of proliferating cell nuclear antigen (PCNA) and nucleolar organizer regions (NORs) in multiple myeloma.

We have studied 72 cases of multiple myeloma (MM) bone marrow trephine biopsies using the monoclonal antibody PC-10 and the colloid silver nitrate method for identification of proliferating cell nuclear antigen (PCNA) and nucleolar organizer regions (NORs), respectively. PC-10 and AgNOR scores were statistically significantly different between low versus intermediate and low versus high grade of malignancy (P < 0.001), whereas their difference was not significant between intermediate and high grade. A strong correlation was identified between these two proliferation-associated indices in each histological grade. There is evidence that the proliferative state of myelomas belonging to the intermediate grade is approximately the same as that observed in high grade (blastic) ones.

Expression of C-myc p62 oncoprotein in multiple myeloma: an immunohistochemical study of 180 cases.

The immunohistochemical expression of C-myc p62 oncoprotein was investigated using the immunoperoxidase method and the monoclonal antibody (Mab) MYC 1-9E10 in bone marrow paraffin sections. 180 cases of multiple myeloma (MM) were studied. C-myc expression was found to correlate well with the grade of malignancy, type of myeloma and tumor cell burden (p < 0.001). A relationship was also observed between C-myc p62 and IgA-secreting myelomas. It was found that intermediate grade myelomas are heterogeneous as far as C-myc expression is concerned. Our findings strongly suggest that C-myc might be involved in myelomutagenesis. The evaluation of its expression in MM may be helpful in determining the grade of malignancy and possibly the biological behaviour of this tumor.

Clear cell sarcoma (malignant melanoma of soft parts). Presentation of two additional cases.

Clear cell sarcoma or malignant melanoma of soft parts is a rare tumor with a predilection for the extremities. Although characterized by a slow clinical course, prognosis is poor because of a high incidence of local recurrences and distant metastases. In this report, two additional cases which originated in the toes are presented.

Proliferating cell nuclear antigen (PCNA) in medullary thyroid carcinoma.

We investigated the expression of proliferating cell nuclear antigen (PCNA) in paraffin sections from 20 cases of medullary thyroid carcinoma (MTC). Follow-up data were available in eleven cases. PCNA index positively correlated with the degree of cellular pleomorphism (grade) of the tumor (p < 0.01), the pathologic stage (p < 0.01) and the poor clinical outcome (p < 0.05). These findings suggest that PCNA may be of prognostic significance in MTC.

Trabecular (Merkel cell) carcinoma of the skin. A case report.

A case of trabecular (Merkel cell) carcinoma of the skin is reported. The lesion appeared on the back, recurred locally twice and metastasized to the intra-abdominal lymph nodes 7 years later. Its unusual primary site, as well as the development of prostatic adenocarcinoma are the main characteristics of the case presented.