Study of growth factors and receptors in carcinoma ex pleomorphic adenoma

Abstract

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor derived from a pre-existing pleomorphic adenoma. It is a good model to study the evolution of carcinogenesis, starting with in situ areas to frankly invasive carcinoma. Growth factors are associated with several biological and neoplastic processes by transmembrane receptors. In order to investigate, by immunohistochemistry, the expression of some growth factors and its receptors [EGF receptor, fibroblast growth factor, fibroblast growth factor receptor 1, fibroblast growth factor receptor 2, hepatocyte growth factor, c-Met, transforming growth factor (TGF) beta1, TGFbetaR-II and insulin-like growth factor receptor 1] in the progression of CXPA, we have used ten cases of CXPA in several degrees of invasion- intracapsular, minimally and frankly invasive carcinoma- with only epithelial component. Slides were qualitatively and semi-quantitatively evaluated according to the percentage of stained tumor cells from 0 to 3 (0 = less than 10%; 1 = 10-25%; 2 = 25-50%; 3 = more than 50% of cells). Malignant epithelial cells starting with in situ areas showed stronger expression than luminal cells of pleomorphic adenoma for all antibodies. Most of the intracapsular, minimally and frankly invasive CXPA presented score 3. However, score 2 was more evident in the frankly invasive one. In small nests of invasive carcinoma, negative cells were observed probably indicating that the proliferative process is replaced by the invasive mechanism. Altogether this data infers that these factors may contribute to cell proliferation during initial phases of the tumor.

A Rare Case of Mucoepidermoid Carcinoma ex Pleomorphic Adenoma arising in Minor Salivary Gland: Histopathological and Immunohistochemical Analysis

“…13 On the other hand, a strong FGF-2 expression was observed in malignant epithelial cells, especially by those from the front invasion islets. As also suggested by Furuse et al (2010), this finding might the importance of this protein in tumor growth, invasion and metastasis. 15 It was very important to know that MEC was the malignant component of this tumor, once CxPA treatment and prognosis are based on the type of the malignant counterpart.…”

“…As also suggested by Furuse et al (2010), this finding might the importance of this protein in tumor growth, invasion and metastasis. 15 It was very important to know that MEC was the malignant component of this tumor, once CxPA treatment and prognosis are based on the type of the malignant counterpart. Patients with MEC are usually treated with surgical resection and have a favorable outcome, with a low metastasis potential; whereas invasive CxPA, as a group, is extremely aggressive with a range of 23 to 50% of the patients developing one or more recurrences and a metastatic rate up to 70% (mainly when tumor capsule penetration exceeds 1.5 mm) So, for a MCxPA presenting frankly invasive characteristics, a complete surgical excision followed by lymph node dissections without radiotherapy complement was performed.…”

Carcinoma ex Pleomorphic Adenoma: A Comprehensive Review of Clinical, Pathological and Molecular Data

“…In cancer of advanced stages, TGFb-1 plays a role in the survival, progression, and metastasis of the entity by encouraging epithelial mesenchymal transition, angiogenesis, and evasion of immune surveillance. While TGFb-1 expression was observed in 10/10 cases examined by Furuse et al [46], it was absent in the epithelial and myoepithelial cells of PA. Transforming growth factor alpha (TGFa) is involved in the maturation and differentiation of keratinocytes.…”

“…This suggests that a paracrine feedback loop is in operation and may be involved in the transition of in situ to invasive carcinoma. While FGFR-1 is expressed in PAs, FGFR-2 is not present in PAs but is strongly expressed in Ca ex PA [46]. This would indicate that it is through FGFR-2 that the effects of FGF-2 in Ca ex PA are mediated.…”

“…HGF-A (scatter factor) and c-Met (a proto-oncogene) play a role in angiogenesis and tumour progression and were strongly expressed in 10/10 cases of Ca ex PA [46]. Similarly IGFR-1, observed in 10/10 cases of Ca ex PA by Furuse et al [46], is often detected in many cancers.…”