RESUMO
The pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are common tumors arising from salivary glands whose histopathology is heterogeneous. The sonic hedgehog signaling pathway (Hh) and signal transducer and activator of transcription 3 (STAT3) play important roles in cell proliferation, favoring tumor growth. The aim of this investigation was to study components of the Hh pathway, as well as STAT3 in salivary gland neoplasms in an attempt to add information about the biological characteristics of these neoplasms. We used 9 cases of PA, 17 cases of ACC, and 20 cases of MEC. Using immunohistochemistry, SHH, GLI1, SUFU, HHIP, and STAT3 were investigated. For comparative purposes, MCM3 (cellular proliferation marker) was also included. In PA, there was high expression of cytoplasmic SHH and SUFU and low expression of STAT3 and MCM3. In the ACC, there was high expression of GLI1, HHIP, and STAT3 and low expression of SHH, SUFU, and MCM3. In the MEC, we observed high expression of SHH, GLI1, SUFU, and HHIP and low expression of STAT3 and MCM3. There was a statistically significant difference between SHH (p = 0.0064), STAT3 (p = 0.0003), and MCM3 (p = 0.0257) when all tumors were compared and a higher expression in parenchyma for all tumors when stroma and parenchyma were compared (p < 0.05). These findings suggests a possible role of Hh pathway in the development and maintenance of the cytoarchitectural pattern of PA, ACC, and MEC, as well as the participation of STAT3 in the development of ACC, irrespective perineural infiltration.
Assuntos
Proteínas Hedgehog/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Transdução de Sinais/genética , Adulto , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Fator de Transcrição STAT3/genéticaRESUMO
The malignant behavior of an ovarian teratoma is related to immaturity, or rarely to the malignant transformation of a somatic component in a mature teratoma (MT). The aim of this work was to review 189 consecutive ovarian teratomas diagnosed between 2006 and 2010 at a public referral center for cancer in Brazil, focusing on cases of MT with malignant transformation. MTs with transformation to squamous cell carcinoma (SCC) were further analyzed by immunohistochemistry for p16 staining. The median age of all patients was 36 yr (mean age, 39.6 yr; SD±4.9). Mature and immature teratomas represented 95.7% (181/189) and 4.2% of the cohort, respectively. Immature teratoma occurred mainly in adolescents under 18 yr. Malignant transformation of the somatic component in MT was observed in 10 of 181 patients (5.5%). SCC was the most common subtype (4/10), followed by differentiated thyroid carcinoma in struma ovarii(3/10), adenosquamous carcinoma (1/10), mucinous intestinal-type adenocarcinoma (1/10), and a well-differentiated neuroendocrine tumor/carcinoid (1/10). Two of 4 SCC cases were strong and diffusely positive for p16, and 2 were negative. In 5 further patients, MT was synchronously observed with other benign and malignant ovarian neoplasms in the ipsilateral ovary (3 mucinous cystadenomas and 1 Brenner tumor) and 1 cystadenocarcinoma in the contralateral ovary. MTs with malignant transformation were larger than those without transformation (P<0.001), but did not demonstrate any association with age. Indeed, our patients with SCC in MT were much younger [median and mean age, 37 and 38 yr (SD±4.9), respectively] than those described previously. As p16 is considered a surrogate marker for HPV infection, the malignant transformation of MT into SSC in young patients raises the possibility of HPV infection as a risk factor in some of these cases. However, molecular studies are needed to clarify the possible role of HPV in the malignant transformation of MT to SCC.