Ljiljana Pavelic

Absence of Retinoblastoma gene product in human primary oral cavity carcinoma

Oral cavity cancer is a major health concern worldwide. Despite advances in surgery, radiotherapy and chemotherapy over the past 35 years, there has been no significant enhancement in the survival of oral cavity cancer patients. Improved survival will require identification of reliable prognostic markers that provide a rational basis for assessment of risk for progression. The altered retinoblastoma (RB) gene has been linked to the hereditary retinoblastoma. This gene is defective in several types of human malignancies. The intent of this study was to evaluate the role of the RB gene in oral cavity tumorigenesis and to explore whether or not there is a relationship between the loss of RB protein and each of several clinicopathological parameters in oral cavity carcinomas. We have analysed the expression of the RB gene in four cell lines (J82, ML1, SaOS2 and WERI-RB-1), 182 oral cavity carcinomas (75 T1 and 107 T3 and T4 lesions) and 55 normal tissues adjacent to cancer by means of an immunohistochemical method and Western immunoblotting. The expression of RB protein was then correlated with clinical outcome in the patients with primary tumours. The significantly higher rate of altered RB expression was found in advanced oral cavity tumours (40 of 107; 37%) in comparison with low grade tumours (9 of 75; 7%). In T3 and T4 tumours, RB gene expression did not correlate with presence or absence of lymph node metastasis, degree of differentiation and patient survival. However, in the T1 cohort, poorer survival rate was seen for those patients who had a tumour with loss of RB protein. This study suggests that tumours in which the RB protein was altered were more aggressive than tumours in which the RB protein was present and that loss of RB protein in oral cavity cancer may be a prognostic variable of tumour progression.

Heterogeneity of c-myc expression in histologically similar infiltrating ductal carcinomas of the breast.

Anti-c-myc monoclonal antibody was used to evaluate the distribution of the c-myc protein in normal and tumor cells of infiltrating ductal carcinoma. A semiquantitative method for reporting immunohistochemical assay results (c-myc score) that enables correlations on a more quantitative basis was used in this study. HL-60 cells demonstrated the strongest nuclear staining when fixed in cold acetone (4° C) for 10 min. All 24 specimens of infiltrating ductal carcinomas of the breast and 7 of 11 samples of normal breast tissues studied revealed the presence of c-myc protein. The level of expression in normal breast tissue was much lower than that in breast cancer. Heterogeneity in expression was found within individual tumors and there were substantial differences in the level of expression among different tumors. The subcellular site of staining was predominantly nuclear, occasionally nuclear and cytoplasmic in the same cell, and rarely only cytoplasmic. All four patients with tumor cells located in close proximity to the ductal basement membrane and over-expressing c-myc protein had positive lymph nodes, suggesting that these tumors are more likely to metastasize.

Utility of anti-carcinoembryonic antigen monoclonal antibodies for differentiating ovarian adenocarcinomas from gastrointestinal metastasis to the ovary

The distinction between primary ovarian tumors and metastatic cancers to the ovary is frequently ambiguous. Recently, we reported that the D-14 monoclonal antibody (MAb), which is directed against a specific epitope of carcinoembryonic antigen (CEA), always reacts with colorectal adenocarcinomas and only rarely with neoplasms of non-gastrointestinal origin [J. Cancer Res. Clin. Oncol. 116, 51-56 (1990)]. We report here an analysis of the reactivity of four different anti-CEA MAbs with formalin-fixed tissue sections of human primary and metastatic colorectal and ovarian carcinomas. The four monoclonal antibodies employed were D-14, CEJ065, ZCEA1, and SP-625. D-14, CEJ065, and SP-625 MAbs reacted with essentially every colorectal adenocarcinoma. In contrast, ZCEA1 was the least reactive and 10 tumor samples showed no reactivity to this MAb. All four anti-CEA MAbs demonstrated scarce immunoreactivity with ovarian carcinomas and appear to be useful for distinguishing between ovarian carcinoma and colorectal metastasis to the ovary. Adenocarcinomas of the stomach and breast were also examined to determine CEA reactivity with the D-14 MAb, since these tumors need to be considered in the differential diagnosis of an ovarian mass. The majority of stomach adenocarcinomas were immunoreactive. In contrast, only 3 of 36 breast carcinomas were weakly immunoreactive, indicating that D-14 MAb is of no assistance in identifying breast carcinoma metastasis to the ovary.

The Role of the p53 Tumor Suppressor Gene in the Tumorigenesis of Inverting Papilloma of the Nose and Paranasal Sinuses

Inverting Papilloma (IP) is a rare neoplasm of the nose and paranasal sinuses. It is considered to be a premalignant lesion as there is a 7–21% incidence of squamous cell carcinoma (SCC) associated with IP. Although there have been many attempts to assign prognostic significance to various features of IP, there has not been a single reliable prognostic indicator identified. Recently it has been shown that mutations of the p53 tumor suppressor gene (TSG) are commonly involved in the process of cancer development. It has been assumed that cells which stain positive with p53 monoclonal antibody (MAb) contain mutant protein due to its lengthened half-life. To better understand the relationship of IP and carcinoma, we analyzed tumor specimens from 12 patients for p53 gene alterations using immunohistochemistry and DNA sequencing. Seven patients had IP without dysplasia, and five patients had IP with dysplasia or squamous cell carcinoma (SCC). All seven patients with IP only had tumors negative for p53 TSG. Three of five patients with IP and dysplasia or SCC stained positive for p53 TSG. No gene alterations of p53 TSG were detected in this study. The role and significance of p53 TSG in the tumorigenesis of IP is discussed based on these findings.