Forty patients with squamous cell carcinoma of the oral cavity were treated with bleomycin prior to undergoing surgery. The degree of the clinical effect of bleomycin and the postoperative clinical course of each case were estimated from the viewpoint of correlation with the mode of invasion. A strong correlation was found among the mode of invasion, bleomycin sensitivity, and clinical course. A slight effect of bleomycin and poor prognosis existed in the group with a diffuse invasion of mode of invasion, while the greatest effect of bleomycin and good clinical course were achieved in the group with a welldefined tumor‐host borderline.

The relationship between the mode of tumor invasion in the tumor-host borderline and the frequency of regional lymph node metastasis was investigated in squamous cell carcinoma of the oral cavity. Cases with grades 1-3 mode of invasion classified by modified Jacobsson criteria showed a low frequency of metastasis (10/72, 13.9%), while those cases with grade 4 mode of invasion, which consisted of grade 4C (cord-like type) and grade 4D (diffuse type) showed a high frequency of metastasis (4C:11/18,61.1%; 4D :9/12,75.0%; total 20/30,66.7%). Moreover, the number of metastatic nodes in each case of mode of invasion ranged from 1 to 3 in grades 1-3, from 1 to 5 in grade 4C, and from 1 to 7 in grade 4D . The presence of metastasis indicated a poorer prognosis than did the absence of the mode of invasion in each grade, especially in grades 4C and 4D .

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BACKGROUND The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5 % of the cases studied (37 of 172 cases). The 5‐year cancer specific survival was 94.0 % for patients without lymph node metastasis, and 51.0 % for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was ‐0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes. Cancer 1997; 80:351‐6. © 1997 American Cancer Society.

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Current clinical success rates of adenoviral vector ( Adv ) -based gene therapy of squamous cell carcinoma ( SCC ) of the head and neck remain unsatisfactory. A major problem with this approach is thought to be related to low Adv transduction efficiency due to weak expression of the adenovirus receptor, coxsackie -adenovirus receptor ( CAR ), in SCC. To improve the limited infectivity of Adv in oral SCC, we constructed mutated Adv incorporating the integrin -binding motif, RGD, in the HI loop of the fiber knob. The mutated Adv infected target cells through integrins commonly expressed in oral SCC. LacZ marker gene expression after infection with this mutated Adv ( Adv -F / RGD ) in oral SCC cell lines that showed reduced expression of CAR was approximately 5 -10 times higher than that obtained with the parental Adv containing wild -type fiber knob ( Adv -F / wt ). In an in vitro study, transduction of oral cancer cell lines with Adv -F / RGD expressing human IL -2 ( AxCAhIL2 -F / RGD ) resulted in greater production of cytokine than AxCAhIL2 -F / wt infection. In an in vivo therapeutic xenograft model of oral SCC in nude mice, AxCAhIL2 -F / RGD demonstrated antitumor effects superior to those of AxCAhIL2 -F / wt. These data suggest that exploitation of genetically altered adenovirus vectors with integrin -binding motifs may offer significant improvements in oral SCC gene therapy.

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