Spindly and Bub3 expression in oral cancer: Prognostic and therapeutic implications.

OBJECTIVES: Bub3 and Spindly are essential proteins required for the activation and inactivation of the spindle assembly checkpoint, respectively. Here, we explored the clinicopathological significance and the therapeutic potential of the opposing roles of the two proteins in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Bub3 and Spindly expression was evaluated by immunohistochemistry in 62 tissue microarrays from OSCC and by real-time PCR in OSCC cell lines and in normal human oral keratinocytes. The results were analyzed as to their clinicopathological significance. RNA interference-mediated Spindly or Bub3 inhibition was combined with cisplatin treatment, and the effect on the viability of OSCC cells was assessed. RESULTS: Overexpression of Bub3 and Spindly was detected in OSCC patients. High expression of Spindly, Bub3, or both was an independent prognostic indicator for cancer-specific survival and was associated with increased cellular proliferation. Accordingly, Bub3 and Spindly were upregulated in OSCC cells comparatively to their normal counterpart. Inhibition of Bub3 or Spindly was cytotoxic to OSCC cells and enhanced their chemosensitivity to cisplatin. CONCLUSIONS: The data point out Bub3 and Spindly as potential markers of proliferation and prognosis, and highlight the potential therapeutic benefit of combining their inhibition with cisplatin.

In vitro histological evaluation of the surgical margins made by different laser wavelengths in tongue tissues.

BACKGROUND: Lasers have become standard tools for the surgical treatment of oral lesions. The purpose of this study is to determine the surgical margins and histologically evaluate the tissue thermal effects induced by different types of surgical instruments. MATERIAL AND METHODS: Cuts were made in pork tongues' mucosa with different lasers (Er:YAG at 2W with and without air / water spray and at 4W with and without air / water spray; CO2 at 3.5W and 7W in pulsed mode and at 7W in continuous mode; the diode laser at 3.5W and boost 3.5W in pulsed mode; Nd:YAG at 6W, 40Hz and electroscalpel at 5W and conventional scalpel as control. Macroscopic and microscopic morphological changes were evaluated. RESULTS: The results of this study showed that the surgical instruments that caused greater tissue damage extension were: the Nd:YAG laser (670.68µm), the diode 3.5W and boost PW (626.82µm), the CO2 7W CW (571.18µm), the CO2 at 7W PW (485.45µm), the diode 3.5W PW (456.15µm), the electroscalpel (409.57µm) and lastly the CO2 laser 3.5W PW (306.19µm) and Er:YAG (74.66µm) laser, regardless of power, mode or air / water spray used. An association between the Tissue Damage Extension and the Degree of Carbonization (r = 0.789; P = 0.01), and an association between the Tissue Damage Extension and Regularity of the Incision were found (r = -, 299; P = 0.01). CONCLUSIONS: The results of this study suggest that lasers can be used in soft tissues biopsies of the oral cavity, enabling a correct histopathological analysis, as long as the biological effects of each laser type are considered. The Er:YAG laser revealed its potential for biopsies of the oral mucosa ensuring a successful histological evaluation and the CO2 laser at 3,5W in pulsed mode presented itself as the best choice for surgeries with hemostasis. Key words:CO2 laser, diode laser, Er:YAG laser, laser surgery, Nd:YAG laser, oral mucosa, thermal effect.

EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survival.

The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P = 0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression (P = 0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS) (P = 0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

Phosphorylated mammalian target of rapamycin is associated with an adverse outcome in oral squamous cell carcinoma.

OBJECTIVES: To evaluate the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and phosphatase and tensin homolog deleted on chromosome TEN (PTEN) in oral squamous cell carcinomas (OSCCs) and relate them with clinicopathologic characteristics and outcome. STUDY DESIGN: We analyzed p-mTOR and PTEN protein expression by immunohistochemistry in 72 OSCCs. Multivariate analysis was conducted to examine their role in survival. RESULTS: p-mTOR expression was observed in 46 (63.9%) cancers and PTEN expression was absent in 22 (30.6%). An adverse independent prognostic value for high p-mTOR expression was found (P = .043) as well as for advanced tumor stage (P = .010) in patients' overall survival (OS). For disease-free survival (DFS), only advanced tumor stage (P = .001) presented an adverse independent prognostic value. CONCLUSIONS: The effect of p-mTOR in OS of OSCC suggests that this marker may serve as a reliable biological marker to identify high-risk subgroups and as a guide to therapy. Furthermore, the high expression of p-mTOR suggests that this protein may be a promising therapeutic target in OSCC.