PNI is a crucial pathological feature for T1-2 oral tongue SCC. Elective neck dissection should be performed in patients who were cN0 with PNI. Careful evaluation for PNI should be advocated in regular pathological diagnosis.

IL-6-IL-6R coexpression was rather high in OSCC, and IL-6 mRNA transcript expression might influence patient survival. The biologic role of IL-6-IL-6R coexpression in OSCC needs additional investigation.

Observation or elective neck dissection (END) for cN0 neck remains controversial for the treatment of T1-2 oral squamous cell carcinoma (OSCC). Perineural invasion (PNI) has been recognized as a poor prognostic factor for OSCC. However, its significance in T1 OSCC remains unclear. A detailed histologic reevaluation of PNI was carried out in 307 patients with T1-2 OSCC who received surgical treatment between June 2001 and January 2009. We found that the presence of PNI correlated with cervical lymph node metastasis in both T1 and T2 OSCC, with a lower PNI-positive rate in T1 (17.1% vs. 36.6%; P<0.001). Importantly, observation for cN0 neck was used twice as often in T1 than in T2 patients (47.4% vs. 22.8%; P<0.001). Although patients with T1 OSCC achieved significantly better outcomes, PNI correlated with neck recurrence and poor disease-specific survival (DSS) only in T1 (P<0.001 and P<0.0001) but not in T2 patients (P=0.399 and 0.1478). Of the 146 patients with T1 OSCC, PNI independently predicted cervical lymph node metastasis, neck recurrence, and poor DSS. END significantly reduced neck recurrence of T1 OSCC in PNI-positive (P=0.001) but not in PNI-negative (P=0.114) patients. In addition, END improved the 5-year DSS of T1 OSCC more in PNI-positive than in PNI-negative patients (16.2% vs. 5.4%). Our results indicate that PNI independently predicts a poor prognosis in T1 OSCC patients who are potentially curable but tend to be treated conservatively. For its efficacy in improving treatment outcomes, aggressive END is indicated for T1 OSCC patients at the presence of PNI.

Head and neck squamous cell carcinoma (HNSCC) is one prevalent human cancer worldwide. No molecular markers are presently used for predicting prognosis in HNSCC. Krü ppel-like factor 4 (KLF4) is a transcription factor with diverse physiological functions, and possesses opposing roles in different human cancers. The expression and roles of KLF4 in HNSCC remain to be elucidated. In this study, immunohistochemical (IHC) analysis of KLF4 in 62 HNSCC was firstly performed. IHC results demonstrated that 42 (67.7%) had decreased KLF4 expression compared with surrounding normal epithelium, while persistent KLF4 expression was demonstrated in 20 (32.3%). The IHC results were further verified by Western blot and real-time PCR analyses to confirm the robustness of staining and interpretation. Interestingly, persistent KLF4 expression independently correlated with a worse disease-specific survival (P = 0.005), especially in patients with advanced disease. In consistent with clinical observation, all five HNSCC cell lines tested revealed a low level of baseline KLF4 expression. Moreover, enforced KLF4 expression in cell line SAS significantly increased in vitro migration ⁄ invasion abilities, multi-drug resistance, and in vivo tumorigenicity. These results clearly illustrate that persistent KLF4 expression predicts poor prognosis and confers aggressiveness in HNSCC. Our data therefore provides valuable information that HNSCC with persistent KLF4 expression might require intensified combination treatment in future practice. (Cancer Sci 2011; 102: 895-902) H ead and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignancy worldwide, and has a profound impact on quality of life.(1) Despite advances in diagnosis and treatment, survival rates of HNSCC have only marginally improved in recent decades.(2) TNM staging system is the current standard for prognostication, which relies heavily on clinical, radiologic and histopathologic parameters. However, substantial heterogeneity is frequently observed in patients of the same risk group. Thus, identifying novel biomarkers will be very useful to improve clinical diagnosis and patient stratification. Krüppel-like factor 4 (KLF4), also known as gut-enriched Krüppel-like factor or epithelial zinc finger, is a zinc finger transcription factor that is physiologically expressed in differentiated epithelium of the gastrointestinal (GI) tract, skin and vascular endothelium.(4,5) KLF4 is primarily regarded as a negative regulator of cell growth, with its ability to regulate the expression of a number of genes involved in cell cycle progression.(6,7) It also plays crucial roles in other physiologic processes, including development, differentiation and tissue homeostasis.(8) Recently, KLF4 has been recognized as one of the genes that can reprogram somatic cells into inducible pluripotent stem cells.(9-11) Overall, these data indicate that the functions of KLF4 are diverse and cell-type specific.Malignant transformation and progression of cancer cells require the accumu...

En bloc esophagectomy may provide a rather satisfactory survival rate for patients with early stage ESCC. However, for patients with distant lymph node metastasis and those with more than three lymph nodes involved, radical surgical resection, even combined with postoperative chemoradiotherapy, cannot improve survival. The prognostic value of biological markers, including PCNA, EGFR, HER-2/neu, and p53, however, is limited.