Expression of claudin, paxillin and FRA-1 in non-nodular breast lesions in association with microcalcifications

Abstract

CONTEXT AND OBJECTIVE: The possible role of adhesion molecules in early breast carcinogenesis has been shown in the literature. We aimed to analyze early adhesion imbalances in non-nodular breast lesions and their association with precursor lesions, in order to ascertain whether these alterations exist and contribute towards early carcinogenesis. DESIGN AND SETTING: Retrospective cross-sectional study based on medical records at a private radiological clinic in São Paulo, Brazil. METHODS:We retrospectively reviewed the medical records of all consecutive women attended between August 2006 and July 2007 who presented mammographic evidence of breast microcalcifications classified as Breast Imaging Reporting and Data System Atlas (BI-RADS) type 4. These women underwent stereotaxic biopsy. Clinical, radiological and pathological data were collected, and immunohistochemical assays searched for claudin, paxillin, FRA-1 and HER-2. RESULTS: Over this period, 127 patients were evaluated. Previous BI-RADS diagnoses showed that 69 cases were in category 4A, 47 in 4B and 11 in 4C. Morphological assessment showed benign entities in 86.5%. Most of the benign lesions showed preserved claudin expression, associated with paxillin (P < 0.001). Paxillin and HER-2 expressions were correlated. FRA-1 expression was also strongly associated with HER-2 expression (P < 0.001). CONCLUSIONS: Although already present in smaller amounts, imbalance of adhesion molecules is not necessarily prevalent in non-nodular breast lesions. Since FRA-1 expression reached statistically significant correlations with radiological and morphological diagnoses and HER-2 status, it may have a predictive role in this setting. RESUMO CONTEXTO E OBJETIVO:A literatura tem mostrado a importância de moléculas de adesão na carcinogê-nese precoce de mama. Objetivamos analisar desequilíbrios precoces de adesão em lesões não nodulares da mama e associação com lesões precursoras, a fim de verificar se essas alterações existem e contribuem com a carcinogênese. . A maioria das lesões benignas mostrou expressão preservada de claudina, associada a paxilina (P < 0,001). Expressões de paxilina e HER-2 foram correlacionadas. Expressão de FRA-1 associou-se à de HER-2 (P < 0,001). CONCLUSÕES: Embora já presente em menor quantidade, o desequilíbrio de moléculas de adesão não é necessariamente prevalente em lesões mamárias nodulares e talvez a expressão de FRA-1 possa ter um papel preditivo neste cenário, uma vez que atingiu correlações estatisticamente significativas com o diagnóstico radiológico e morfológico e com o status de HER-2.

Role of the Transcription Factor FOSL1 in Organ Development and Tumorigenesis

“…On the contrary, FOSL1 is detectable only in one-third of the primary low-grade breast tumors. In this respect, only ~10% of the preserved ductal cells of these tumors are positive for FOSL1 [9,91]. In premalignant non-nodular breast lesions, FOSL1-specific staining is always evident around ductal structures in the proximity of the basal membrane [91], whereas healthy ductal cells are usually FOSL1-negative.…”

“…In this respect, only ~10% of the preserved ductal cells of these tumors are positive for FOSL1 [9,91]. In premalignant non-nodular breast lesions, FOSL1-specific staining is always evident around ductal structures in the proximity of the basal membrane [91], whereas healthy ductal cells are usually FOSL1-negative. In addition, non-proliferative lesions, including papillary lesions, apocrine metaplasia, and columnar alterations, are also FOSL1-negative.…”

“…For instance, the neoplastic cells of the advanced TNBC and atypical malignant tumors usually exhibit moderate-to-strong nuclear staining for FOSL1 [90]. At the same time, the differences in FOSL1 levels and copy numbers between HER2-enriched and TNBC are not significant [91][92][93]. The highest FOSL1 expression occurs in metastatic lesions of lymph nodes where it is about 50% higher than non-metastatic tumors.…”

Evaluation of Paxillin Expression in Epithelial Dysplasia, Oral Squamous Cell Carcinoma, Lichen Planus with and without Dysplasia, and Hyperkeratosis: A Retrospective Cross-Sectional Study

“…Furthermore, the study has shown that patients with OSCC developed on a previous OLP lesion have a higher recurrence rate when compared with primary OSCC [65]. Recent research has also shown that a high suprabasal intensity level of paxillin in ED, rather than in OSCC, may be associated with early appearances in oral carcinogenesis since the frequency of paxillin suprabasal intensity in invasive types of cancer was estimated to be lower than the frequency of these in potentially cancerous lesions (p = 0.001) [55]. This outcome validated the result reported in the study by Madan et al [58].…”

“…In addition, cell adhesion molecules play a role in adhesion and function as tumor suppressors [54]. Disorganized cell-cell or cell-extracellular matrix (ECM) attachment can significantly be provided towards unmanaged cell proliferation and progressive deformity of normal tissue construction [55]. Therefore, its expression in benign lesions is an essential factor that should be explored.…”