| Summary: | 博士 === 國立臺灣大學 === 病理學研究所 === 104 === For the patients with advanced oral cancer disease, the treatment outcomes and disease control under current therapy are disappointed. For the clinicians, it is still full of challenges and difficulties need to be overcome when facing the advanced oral cancer disease. In our opinion, how to identify the risk of failure and its underlying mechanism from the pathological findings were of paramount importance. Therefore, the main purpose of our study was to identify the possible and specific pathological expressions from the worst patients with advanced oral cancer disease, the patients with positive extranodal extension (ENE) and/or pretreatment tumor necrosis.
We retrospectively reviewed 218 eligible patients with stage III/IV oral squamous cell carcinoma (OSCC) and neck lymph node metastasis and also had received comprehensive treatment at our department between January 2004 and December 2011. The 5-year disease-free, disease-specific and overall survivals of all the patients in our series were 33.5%, 35.8% and 33.8%, respectively. In the first part of our study, we focused on the specific pathological expression in extranodal tumor. First, we noted that the nuclear phosphorylated mammalian target of rapamycin (p-mTOR) expression was highly associated with differentiation of OSCC. The moderately and poorly differentiated OSCC always demonstrated varying degrees of nuclear p-mTOR expression. By the discrimination from pathological expression of extranodal tumors, the 5-year disease-free survival of the patients without ENE, with and without nuclear p-mTOR expression in extranodal tumors was 54.3%, 23.4% and 55.2%, respectively. The 5-year overall survival of the patients without ENE, with and without nuclear p-mTOR expression was 55%, 18.7% and 51.3%, respectively. After the stratification of multivariate analysis, the nuclear p-mTOR expression in extranodal tumors was a significant independent adverse factor for disease control and treatment outcome. Its expression in extranodal tumors could add more significant information in traditional ENE grading system.
In the second part of study, we focused on the specific pathological expression of hypoxic OSCC surrounding necrosis. First of all, the necrosis finding in pretreatment magnetic resonance imaging (MRI) image had great association with pathological cystic necrosis. Both of them had substantial positive association (kappa value 0.64) in metastatic lymph nodes. Then, we always noted that hypoxic OSCC surrounding necrosis, either in primary tumor or metastatic lymph nodes, frequently showed colocalized expression of and immunohistochemical associations between Hypoxia-inducible factor-1α (HIF-1α) and programmed death ligand 1 (PD-L1). There were moderate (kappa value 0.54) and almost perfect (kappa value 0.86) positive association between positive HIF-1α and PD-L1 expression in primary tumor and metastatic lymph node, respectively. Finally, the patients with both necrosis and positive PD-L1 expression in OSCC surrounding necrosis had worse treatment outcome and disease control. The dissemination of these hypoxic and immune-privileged positive PD-L1 tumor cells may play an important role for the worse disease control, especially the worse distant disease control.
In conclusion, we found that both the positive nuclear p-mTOR expression in extranodal OSCC and positive PD-L1 OSCC surrounding necrosis had significant relation with disease control and treatment outcomes. Among the patients with advanced OSCC disease, the patients with either of two specific pathological expression must be worth of the target for basic or clinical studies in the future.
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