A wide variety of virally and spontaneously transformed fibroblasts secrete a major transformation-related phosphoprotein with a molecular weight (MW), depending on the species of origin, of about 62,000 (62K). Markedly elevated extracellular levels of this major 32P-labelled protein are not simply linked to exponential growth but instead are associated directly with transformation. The phosphoprotein is not antigenically related to p60src, p60c-src or simian virus 40 (SV40) non-viral T antigen, and it is further distinguishable from SV40 non-viral T antigen (pp 53) on the basis of its electrophoretic mobility. In this study we have compared a variety of normal and transformed epithelial cells for secretion of this 32P-labelled protein and have found that this marker distinguishes neoplastic from preneoplastic and normal mouse mammary epithelium and also identifies highly tumorigenic cells derived from guinea pig bile duct epithelium and rat liver epithelium. Because the classical phenotypic properties commonly associated with transformation of fibroblasts cannot be generally used to discriminate tumorigenic from non-tumorigenic epithelial cells, this phosphoprotein, which identifies tumorigenic cells of both fibroblastic and epithelial origin, is likely to be of particular importance.

The actin cytoskeleton underlies several normal cellular functions and is deranged during carcinogenesis. Gelsolin, a multifunctional actin-binding protein, is downregulated in several types of tumors and its abnormal expression is one of the most common defects noted in invasive breast carcinoma (ICA). This study utilizes immunohistochemistry to examine the expression of gelsolin in 95 ICA, 59 ductal carcinoma in situ (DCIS) and 36 benign lesions, including 17 atypical ductal hyperplasia (ADH). Cytoplasmic staining was scored as positive, reduced or negative. Gelsolin expression was then correlated with patient's age, tumor size, histologic grade and lymph node status. All unremarkable breast biopsies, 88% of ADH, 44% of DCIS and 28% of ICA were positive for gelsolin. This represents a significant difference among the groups (p = < 0.0001) and the trend towards reduced gelsolin with the progression to ICA is significantly linear (p = < 0.0001). For invasive carcinoma, patients older than 44 years were significantly more likely to have decreased expression of gelsolin than patients 44 years old and younger (p = 0.007). Bivariate analysis showed no correlation of gelsolin expression with lymph node status (p = 0.62), tumor size (p = 0.10), histologic grade (p = 0.42), estrogen receptor status (p = 1.0) or other clinicopathologic parameters. In clinical follow-up, there were 18 breast tumor related deaths within a median follow-up time of 4.2 years. Survival analysis indicated that the level of gelsolin expression may be associated with survival (p = 0.06). In summary, the frequency of gelsolin deficiency increases significantly with progression from ADH to DCIS to ICA. Additionally, gelsolin expression may be an independent marker of prognosis.

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The majority of the adenocarcinomas arising in Barrett esophagus manifest clinically at an advanced stage and have a poor prognosis. As a result of this poor prognosis, much attention has been directed toward the exploration of markers for neoplastic progression in Barrett esophagus. The objective of the present study was to determine the expression of beta-catenin by immunohistochemical analysis in 70 adenocarcinomas developed in Barrett esophagus and to examine its relationship to various prognostic factors currently in use. Abnormal beta-catenin expression, consisting of the loss of membranous staining and the appearance of the nuclear staining, was found in 43 cases (61%). Of patients with the 43 tumors showing abnormal beta-catenin expression, 25 (58%) survived more than 1 year. In contrast, only 7 (26%) of 27 patients with tumors showing normal beta-catenin expression survived longer than 1 year. Most of the superficial (Tis-T1) tumors (83% [10/12]) exhibited abnormal beta-catenin expression compared with only 53% (31/58) in the T2-T3 group. These results suggest a possible correlation among beta-catenin expression, tumor stage, and length of survival as prognostic factors in patients with adenocarcinoma in Barrett esophagus.