Squamous Cell Carcinoma Transformation Research Articles

Sequential immunohistochemical p53 expression in biopsies of oral lichen planus undergoing malignant evolution.

Transformation in squamous cell carcinoma (SCC) may occur in a small percentage of patients affected by oral lichen planus (OLP), but the pathogenesis remains to be elucidated. Overexpression of p53 protein was investigated immunohistochemically in 28 cases of OLP, followed up by sequential biopsies for up to 96 months. In 15 cases (Group 1), no dysplastic changes or neoplastic transformation occurred during the follow-up period; in 7 cases, OLP and SCC were synchronously observed (Group 2), whereas in another 6 cases (Group 3) SCC developed several months or years after diagnosis of OLP. The percentage of p53-positive epithelial cells at first diagnosis was significantly higher in the cases of Groups 2 and 3 than in those of Group 1. In contrast, evaluation of growth fraction by MIB-1 monoclonal antibody did not show any statistical differences among the three groups. Although no conclusions can be drawn about the molecular pathway leading to neoplastic transformation of OLP, or about the role of p53, the results indicate that immunohistochemical evaluation of p53 expression may be a practical tool to select cases of OLP with a high risk of neoplastic transformation.

Genes differentially expressed with malignant transformation and metastatic tumor progression of murine squamous cell carcinoma

Molecular changes occurring with tumor formation and metastasis need to be identified in order to define novel markers and targets for chemoprevention and therapy. Cell lines from a multistage model of murine squamous cell carcinoma were analyzed for differences in gene expression using mRNA differential display. mRNA was isolated from primary keratinocytes, an in vitro transformed keratinocyte line (Pam 212), and three metastatic cell lines derived from Pam 212 following tumor progression in vivo. cDNA was synthesized by reverse transcription and amplified by PCR using 72 primer combinations to screen and compare approximately 3,600 sequences. Five cDNAs with a differential expression pattern confirmed by Northern blot analysis were cloned and sequenced, revealing homology with known genes. The gene encoding tropomyosin alpha was preferentially expressed in primary keratinocytes; genes for tyrosine kinase Yes-associated protein (YAP65) and ribosomal protein L18a were preferentially expressed in transformed and metastatic tumor cell lines; and genes for the Gro-alpha family cytokine KC and antigen Sp17 exhibited increased expression in the three metastatic cell lines. The structure and function of the genes identified suggest that they may possibly be linked to cell shape and motility, signal transduction, protein synthesis, growth, granulocyte chemotaxis, and angiogenesis. This study demonstrates the ability of mRNA differential display to detect altered gene expression in this tumor progression model of murine squamous cell carcinoma, and the potential usefulness of this approach for identification of candidate genes as chemoprevention markers and targets.

Genes differentially expressed with malignant transformation and metastatic tumor progression of murine squamous cell carcinoma

Genes differentially expressed with malignant transformation and metastatic tumor progression of murine squamous cell carcinoma

Intracellular diacylglycerol: a mitogenic second messenger proposable as marker of transformation in squamous cell carcinoma of the lung

In this study, we examined 50 patients with documented lung cancer projecting in the bronchial lumen unilaterally. Bronchial lavage from the affected and unaffected sides provided neoplastic and normal cells in which we studied an intracellular mitogenic second messenger, diacylglycerol, associated with transformation. The levels of diacylglycerol in cells from the affected side were compared with that from the healthy side, thus providing an internal control for each patient. Our data show that the levels of diacylglycerol in lavage fluid relative to affected bronchus are elevated in 56% of all the patients examined. This elevation reaches 77% in patients with squamous cell carcinoma, a value of sensitivity higher than ‘traditional’ markers for cancer of the lung. Thus, these findings may have significant implications for the use of diacylglycerol measurement as a novel biomarker for early detection of lung cancer, and for monitoring recurrences after treatment.

Immunolocalizations of human gelatinase (type IV collagenase, MMP-9) and TIMP (tissue inhibitor of metalloproteinases) in normal epidermis and some epidermal tumors.

The matrix metalloproteinases (MMPs) MMP-2 and MMP-9 (gelatinases) have been suggested as serving an important role in cleaving the basement membrane structure. Tissue inhibitors of metalloproteinases TIMPs (particularly TIMP-1) are known to inhibit MMPs. Based on this background, we raised monoclonal antibodies against human gelatinase (MMP-9) and human recombinant TIMP (TIMP-1), and immunostained these two components in skin from patients with squamous cell carcinoma (SCC), Bowen's disease (BD) and keratoacanthoma (KA). MMP-9 showed positive staining mainly in the granular layer of normal epidermis. In some cases of SCC and BD, MMP-9 showed positive staining in the dysplastic lesions even in the basal layer. TIMP showed a thorough positivity in normal epidermis. Unstained regions with this antibody were observed in SCC and BD. These results suggest that an altered staining pattern for MMP-9 and TIMP may be closely related to the malignant transformation of SCC and BD.

1092 Intracellular diacylglycerol: A mitogenic second messenger proposable as marker of transformation in squamous cell carcinoma of the lung

We examined 50 patients with unilateral lung cancer. Bronchiallavage provided neoplastic and normal cells in which we studied a mitogenic second messenger, diacylglycerol, that is associated with early stages of transformation. Level ofdiacylglycerol in cells from the affected side was compared with that from the control side, thus providing a control for each patient. Diacylglycerol in lavage fluid from the affected bronchus was elevated in 60% of the patients. This elevation reached 73% in patients with squamous cell carcinoma, a sensitivity higher than “traditional” markers for lung cancer. These findings may have significant implications for the use of diacylglycerol as a novel marker for early detection of lung cancer, and for monitoring recurrences.