The role of surgical pathology in treatment of the oral cancers is described. Some of device techniques to treat the biopsied and resected specimens of oral cancers are introduced in this paper. Surgeons and pathologists should discuss frequently to lead the accurate pathological diagnosis.

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In order to evaluate vascular invasion ( VI ) and perineural invasion (PNI) as histopathologic parameters for predicting prognosis of oral cancer, step sections of 51 lesions surgically removed from 48 patients with previously untreated squamous cell carcinoma of the tongue were examined. To accurately identify the vascular lumen, and eliminate false positives due to artifacts, VI was assessed immunohistochemically using antisera against factor VIII and CD31, because these antisera detect endothelial cells. Additionally, elastic fiber staining was used for detection of tumor emboli in blood vessels.
VI and PNI were detected in 9 (17.6 % ) and 7 (13.7 % ) lesions, respectively. Of the 9 VI -positive lesions, 4 lesions showed lymphovascular invasion (ly), and all 9 showed intravenous invasion (v) . All Ti lesions and tumors less than 4 mm in depth were negative for both VI and PNI. However, the incidence of VI was significantly higher in tumors more than 10 mm in depth than in those less than 9 mm in depth (p<0.01) . Clinically, tumors with VI showed higher incidence of cervical metastases than those without VI, but this was not statistically significant. Tumors found to be v ( + ) ⋅ly ( + ) had a significantly higher incidence of postoperative locoregional recurrence than those found to be v ( - ) ⋅ly ( - ) (p<0.05) . Incidence of PNI tended to correlate with tumor depth, but this was not of significant prognostic value. Because of the low incidence of VI itself, the prognostic value of v and ly was not clarified in this study. The present authors believe that a multiinstitutional study, using the precise definitions of v and ly, could be an effective means of clarifying their significance.

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Eity-three patients with squamous cell carcinoma of the oral tongue (Stage I : 22, early Stage II : 18, advanced Stage II : 13, Stage III : 23, Stage IV : 7) were studied histologically on the resected tumor speciments and the following results were obtained.
1. In the patients with early tongue carcinoma treated with only surgery, 1) the deep surgical margin seemed to be more associated with the postoperative local recurrence than the lateral surgical margins and the tumor-free margin may be necessary to have of at least 10 mm, considering the tissue shrinkage. 2) the maximum tumor size and thickness had their relationship and T1 tumors (<20 mm in size) seemed to be about 5 mm thick. 3) the surgeons should take a prudent attitude to the pattern of tumor invasion in the primary tumor resection.
2. In the patients with advanced tongue carcinoma treated with preoperative chemoradiotherapy followed by surgery, the patterns of distribution of residual viable tumor cells in the primary tumor after preoperative treatment seemed to have a great influence on the local recurrence.

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Much information like depth of invasion was required owing to the advance of therapy for oral cancer. However, the handling of the surgical material as a base of the pathological examination still is not standardized. In this paper, our sampling method for Breadloaf step sectioning (BLSS) was described in order to standardize of the pathological observation of the tongue cancer. In our pathological report, the size of the cancer (pT), atypical epithelia of the surgical incisional margin (dys), the depth of invasion (depth) and the relation of the depth of invasion and the extent to the lateral side (ie) were added to mandatory procedure. Furthermore, the cooperation of both the oral surgeon and the oral pathologist in order to utilize BLSS was described.

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One hundred and two cases, diagnosed as squamous cell carcinoma of the mandibular gingiva, were clinicopathologically examined. According to the mode of mandibular invasion, all cases were histologically classified two groups : 1) expansive type (80%) and 2) invasive type (20%) . The expansive type carcinomas were found to have a well-defined smooth borderline, while the invasive type had a diffuse irregular margin with infiltrative growth pattern.
These two histopathological types of mandibular gingival carcinoma were compared. The histopathological types were closely associated with radiographical types of mandibular resorption, pressure and moth-eaten types. The cases of expansive type showed radiologically pressure type (70%) and moth-eaten type (30%), and all cases of invasive type showed moth-eaten type. Histologically, the bone resorption was occurred befor carcinoma invasion in the expansive type. On the other hand, in the invasive type the bone resorption was occurred after carcinoma invasion or synchronously. In the expansive type Howship's lacunae in the reformation phase were relatively marked, while a large number of Howship's lacunae in the resorption phase were observed in the invasive type. Especially, histological examination showed that the intra-mandibular canal inf iltrasion without bone resorption was revealed in cases of invasive type, only. The 5-year survival rate of total cases was 75% in the expansive type and 32% in the invasive type.
These results suggested that the histopathological types of mandibular carcinoma, expansive and invasive types, were useful classification for oral oncologists.

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This research was conducted to better understand the relationship between observations of tongue carcinoma using enhanced CT images and the effects of preoperative treatment. We created a comparative review of the effects of contrast images and preoperative treatment as well as histologic findings, using the enhanced CT images of 10 instances, of tongue squamous cell carcinoma after preoperative treatment and surgical removal of the primary site.
It was observed from the enhanced CT images that there was a tendency for the more intense the contrast effect before the preoperative treatment, the more effective the histologic treatment. In terms of histology, these cases had the tendencies of having stronger lymphocytic infiltration and more blood vessels. In a case where the preoperative treatment reduced the contrast effect, the reduction of lymphocytic infiltration and blood vessels, which was coincident with increased fibrous interstitial, was observed. In a case where the contrast effect intensified, an increase of granulation tissue with an abundant blood vessels was observed. These results showed that the enhanced CT images reflected an observation of interstitial tissues and suggested that the changes of the enhanced CT images as a result of the preoperative treatment reflected the histological change.

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In this study, We examined the utility of MRI diagnosis concerning the tumor extent in the primary lesion of tongue cancer in comparison with other manipulations. The subjects were 42 patients who had received a surgical intervention for S. C. C. of the tongue graded T2-T4 and examined by MRI and CT. The sensilivity by MRI was 90.9% which was significantly higher than the value by CT of 35.1%. Among T1WI, T2WI and T1Gd-DTPA, showed the highest sensilivity. As for the difference in the tumor extent indicated by MRI and by palpitation in relation to the actually resected tumor, no difference was observed between MRI and palpitation. In the histopathological finding as compared with MRI, however, MRI could recognize the shorter diameter about 40-50% and the depth about 60-70% as large as those recognized by histopathological examination.

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Dynamic enhanced magnetic resonance imaging (MRI) of 40 patients with squamous cell carcinoma of the tongue was performed to investigate the correlation between the margin of the surrounding tongue musculature and clinico-histopathological features. T1 weighted spin echo sequence (TR/TE = 200/20) coronal plane images were obtained. The signal intensity of the operator-defined region of interest (ROI) was measured and the signal enhancement to noise ratio (SE / N) calculated. Slices taken at the time of maximum SE/N were used for evaluation (both clear and unclear types) . T stage, growth pattern, pattern and stage of invasion, and lympho-plasmocytic infiltration were correlated to the marginal appearance on enhanced MRI. The results were as follows
1. There were more cases of unclear type than clear type tumor.
2. Clinically, endophytic tumors tended to show an unclear marginal appearance compared to that of exophytic and superficial tumors on enhanced MRI.
3. Histopathologically, the pattern of invasion had a significant correlation to marginal appearance on enhanced MRI (P<0.01) .
The results of our study suggested that marginal appearance on enhanced MRI could be an important factor for defining the area of tumor infiltration.

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To assess the malignant potential of the tongue cancer by intraoral ultrasonography (US) and MR imaging (MRI), we examined 57 patients with squamous cell carcinoma of the tongue. Intraoral US using 7. 5M Hz linear microprobe and MR findings on Gd-DTPA enhanced T1-weighten image were examined with respect to the shape, the border, the internal signals, and the depth of invasion, respectively. On the intraoral US, 53 of 57 tumors (93.0%) excepting lesions less than 1 mm of pathologic depth of invasion were detected. On the other hand, tumor detection rate on the MRI was 89.0% . There were significant relationships between US findings and invasion and stromal reaction. Tumors invading diffusely in scchirous stroma exhibited irregular shapes, diffuse borders, and heterogeneous internal signals on the US. In addition, tumors invading 8.0 mm or more on US and MRI had developed neck metastasis in those less than 8.0 mm in the depth of invasion. Thus these US findings provide an useful information to predict the incidence of occult neck metastasis clinically N0 tumors. In conclusion, intraoral US combination with MRI is effective to evaluate tumor extent and its malignant potential. In case of excisional biopsy, particularly, the preoperative intraoral US should be performed routinely.

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Objective: To clarify the diagnostic accuracy of CT in detecting the extent of tumor invasion into the surrounding soft tissues by squamous cell carcinoma of the mandibular gingiva.
Method: Axial CT scans of 77 patients with carcinoma of the mandibular gingiva were evaluated by three Oral and maxillof acial radiologists for the tumor invasion into the surrounding soft tissues. All patients underwent excision of the tumor in Kyushu University Dental Hospital from 1992 to 1999, and the presence and the extent of tumor invasion were confirmed by the macroscopic or histopahological findings following surgery. The observers rated their level of confidence for the presence of tumor invasion into genioglossus muscle (GGM), mylohyoid muscle (MHM), intrinsic lingual muscles (ILM), internal pterygoid muscle (IPM), masseter muscle (MM), labiobuccal tissues (LBT), and platysma muscle (PM) on the following five-point scale : 1, negative ; 2, probably negative ; 3, unsure ; 4, probably positive; 5, positive. The mean ROC curve area (Az) of each observer for tumor invasion into each tissue was obtained, and used as the index of diagnostic accuracy.
Results : The mean Az values for the detection of tumor invasion on CT was 0.86 for GGM and IPM, 0.82 for MHM, 0.80 for MM, 0.76 for ILM, 0.71 for LBT, and 0.65 for PM.
Conclusion : We should carefully interpret the tumor invasion into ILM, LBT and PM on CT images referring to the various clinical information, including inspection or palpation.

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To examine whether the thickness of a primary tumor in patients with tongue carcinoma would be able to predict the potential for subsequent cervical lymph node metastases with ultrasonographic (US) examination, consecutive 30 patients with sonographically N0 tongue carcinoma were studied. Lymph nodes were evaluated with a 10MHz mechanical sector transducer. The thickness of a primary tumor was measured with a 7.5 MHz convex intraoral transducer or with a postcontrast CT scan, when an intraoral transducer was unable to be applied.
Of 30 patients 15 underwent neck dissections. Of these patients, 10 were proved to be pathologically positive and remaining 5 were negative. The remaining 15 patients who were not performed neck dissection were considered to be negative because there was no evidence of metastasis during a follow-up period of 2 years at shortest. Therefore, we finally determined 10 patients were positive and remaining 20 were negative. The final US diagnosis indicated US examination performed just before operation or that obtained most recently in patients without neck dissection. The sensitivity, specificity and accuracy for metastasis of the final US diagnosis were 90%, 95% and 93%, respectively. The tumor thickness varied from 0.3 to 2.0cm. Using 1.0 cm as a cut-off thickness, the sensitivity, specificity and accuracy for metastasis of the initial US diagnosis were 70%, 85% and 80%, respectively.
It was indicated that 1.0 cm was the most appropriate cut-off thickness for predicting occult lymph node metastases in patients with sonographically N0 tongue carcinoma. However, diagnostic reliability was less sensitive or specific than the final US diagnosis. We deemed that a“watchful waiting”policy might be better than elective treatment if follow-up US examination could be performed carefully and periodically.

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Incisional biopsy is routinely performed to determine their malignancy; however, incision into a neoplasm could help it to spread or could even increase its malignancy. Because direct inspections and digital palpations are possible for lesions of the oral cavity, close examination by surgeons make it possible to determine the malignancy of the lesion. Thus, we employ excisional biopsy for small and localized oral carcinomas as surgical treatment directing at controlling the primary tumor, to prevent spreading cancer cells by incisional biopsy. In our principles, we adopt excisional biopsy for oral carcinomas, which could be effectively treated with simple excision of the primary lesions. To determine their malignant potential, we evaluate the depth of invasion by intraoral ultrasonography (usD) based on the clinical growth pattern. Superficial and exophytic tumors less than 15 mm in usD should be simply excised combined with vital staining with Lugol. Furthermore, endophytic tumors less than 8 mm in usD could be treated by excisional biopsy with preoperative chemotherapy. To obtain tumor-free margins, we have performed concave or box-shape excision combined with intraoperative rapid frozen section diagnosis. In conclusions, excisional biopsy is an effective treatment to improve prognosis and quality of life of the patients with oral carcinoma.

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Sixty-two patients with tongue carcinoma who underwent an excisional biopsy were retrospectively examined with respect to the correlation between clinical findings (tumor size, growth pattern) and histopathological findings (tumor depth, mode of invasion) . Using the growth pattern proposed by Washizu, it was found that deeply infiltrating type tumors were the most invasive, and some granular type tumors were deep. The endophytic type tumors showed a positive correlation between tumor size and tumor depth. Furthermore, most of the exophytic type tumors revealed low grade malignancy, while highly invasive carcinomas were more prevalent in the endophytic type tumors. Therefore, in the endophytic type tumors a sufficiently deep margin must be chosen based on detailed clinical observation.
As a result, we were able to obtain 100% local control rate and the 5-year cumulative survival rate for all patients was 94.6%. We are led to the conclusion that excisional biopsy for early tongue carcinoma is both beneficial and safe.

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The purpose of this study was to assess the clinical course of stage I, II oral squamous cell carcinoma and relevant prognostic factors by reference to treatment modalities : (1) excisional biopsy (EB) and (2) incisional biopsy followed by preoperative chemotherapy (IB+chemo) . A total of 185 patients were entered into this retrospective study. Sixty-one patients underwent EB, and 124 patients IB+chemo. The clinical outcome of these two patient groups were compared. The chemotherapeutic effects in IB+chemo patients according to the Oboshi and Shimosato classification were as follows: 32 patients, grade III or N ; 48 patients, grade II b ; 44 patients, grade I or II a. The incidence of primary recurrence and regional lymph node metastasis was high in patients with grade I or II a compared with patients with EB. This results was statistically significant with univariate and multivariate analysis. Furthermore, the grade of chemotherapeutic effects compared with EB was selected as an independent prognostic factor for survival by multivariate analysis using Cox proportional hazard model. Grade I or II a of chemotherapeutic effect was associated with recurrence at primary site, regional lymph node metastasis, and a worse survival rate.

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Around oral squamous cell carcinoma (SCC), the expanding epithelial dysplasia are often observed. They are considered to cause local recurrence or second primary cancer. Especially, these epithelial dysplasia are found frequently in superficial lesion which are the objects in excisional biopsy. The aim of this study is to evaluate the usefulness of decision for surgical margin by iodine staining. 49 primary cases with tongue SCC were treated by excisional biopsy. They were divided into 2 groups, A group (no iodine staining group) with 25 cases and B group (iodine staining group) with 24 cases. And they were compared.
We obtained the following results:
In regard to local recurrence, there are 4 cases (16%) at A group, 1 case (4.2%) at B group. Epithelial dysplasia positive in margin status by rapid frozen section diagnosis were observed 8 cases (32%) in A group, 2 cases (8.2% ) in B group. Therefore, in deciding the surgical margin of excisional biopsy, the staining with iodine solution is useful.

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Membranous expression of E-cadherin and catenins were evaluated in f ormalin fixed, paraffin embedded biopsied specimens from a series of 135 squamous cell carcinoma (SCC) of the oral cavity by immunohistochemical methods using monoclonal antibodies. Loss of normal membranous E-cadherin, α-, β- and γ-catenins expression was found in 55%, 66%, 61%, and 59% of the tumors, respectively. Univariate analysis revealed that aberrant membranous expression of E-cadherin and α-, β-, and γ-catenins correlated significantly with type of growth (P=0.007, =0.001, =0.0002, and =0.001, respectively), mode of invasion (P=0.014, =0.01, =0.003, and =0.02, respectively), clinicopathological malignancy grading (P=0.002, =0.003, =0.0001, and =0.002, respectively), and pathologically proven lymph node metastasis (P<0.0001, <0.0001, <0.0001, and <0.0001, respectively) . Moreover, survival estimates differed significantly for preserved and reduced expression of E-cadherin (P0.01), α-catenin (P=0.01), β-catenin (P = 0.0006), and γ-catenin (P0.006) . = Regarding to predict tumor metastasis and survial, however, multivariate analyses demonstrated that evaluations of N category and TNM stage were more clinically useful than that of immunohistochemical detection of E-cadherin and catenins. However, when investigation was carried out in stage I and h oral SCC, a siginif icant correlation was observed between reduced expression of E-cadherin and catenins, but not clinicopathological variables, with lymph node metastasis. The immunohistochemical detection of E-cadherin and catenins is clinically useful, especially for selecting patients who may develop lymph node metastasis in early stage oral SCC.

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The adhesion protein E-cadherin plays an important part in the process of epithelial morphogenesis. Expression of this protein is down regulated during the acquisition of metastatic potential in the late stages of epithelial tumor progression. There is evidence for transcriptional blockage of E-cadherin gene expression in this process. The transcription factor snail, which is expressed by f ibroblasts and some E-cadherin-negative epithelial tumor cell lines, represses transcription of E-cadherin. Metastasin (also referred to as mts-1, S100A4) in the control of cell motility as well as in cancer invasion and metastasis has now been extensively studied in numerous tumors. In this study, we examined the expression of E-cadherin, related proteins, snail and metastasin by western blot and RT-PCR in the oral squamous cell carcinoma cells. Immunohistochemical staining of oral squamous cell carcinomas was conducted to identify metastasin. It was found that E-cadherin was not recognized in 4 cell lines in grade 4D. RT-PCR analyses showed that snail and metastasin were expressed strongly in grade 4D cell lines. By immunohistochemical analysis, metastasin was highly detected in invasive cases. It is concluded that cell-cell adhesion would be decreased, and that E-cadherin may plays an important role in the process of invasion and metastasis. Snail further represses transcription of E-cadberin, and metastasin correlates with tumor invasion and metastasis in oral squamous cell carcinomas.

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Loss of cell-cell adhesion and degradation of extracellular matrix are necessary for infiltration and metastasis of cancer cells. E-cadherin is a calcium-dependent cell adhesion molecule and the loss of E-cadherin expression has been reported in highly invasive sequamous cell carcinomas (SCCs) . Recently, a transcription factor Snail was identified as repressor of E-cadherin. In this report, we found that HOC719, a cell line derived from oral SCC, expressed E-cadherin heterogeneously and we isolated E-cadherin positive (HOC719-PE) and negative cells (HOC719-NE) from this cell line. HOC719-PE cells showed epithelial cell shape, while HOC719-NE cells showed fibroblastic. Moreover, HOC719-NE cells had higher invasive ability and expressed MMP-2 and Snail mRNA more strongly than HOC719-PE cells. Then we studied the effects of Snail expression in E-cadherin positive cells by transfecting a Snail expression vector. E-cadherin promoter activity decreased in transiently Snail transfected A431 and HOC719 - PE cells. Stably Snail-expressing A431 cells changed to the fibroblastic morpbology and acquired more invasive ability. By the RT-PCR analysis, these Snail-expressing cells showed decreased expression of E-cadherin but increased expression of MMP-2. Furthermore, overexpressing of Snail induced the increased MMP-2 promoter activity of A431 and HOC719-PE cells by the luciferase reporter assay.
These results indicate that Snail plays a key role in the acquisition of more invasive phenotypes of SCC via changing the cell shape and expression of E-cadherin and MMP-2.

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Establishment of the cell line with highly lymph node metastatic potential is necessary for analysis of the mechanism of lymph node metastasis of squamous cell carcinoma of the tongue. We succeeded in establishment of oral squamous cell carcinoma cell lines with highly lymph node metastatic potential by repetition of orthotopic implantation to the tongue of the nude mice using human oral squamous cell carcinoma cell line (SAS, BSCC) . We also report some results of the analysis for characterization of these cell lines.
Two cell lines with higly lymph node metastatic potential showed 100% of transplantation ratio and metastasis to the cervical lymph node ratio, and their ability which are growth, random migration, invasion were sytronger than the original cell lines, and especially, accentuation of invasion ability was remarkable. Though in immunof luorescence antibody method, E-cadherin, β-catenin, FAK were also slightly positive in either cell line, the difference of the localization was not clear. In the analysis by the Western blotting method, there was the increase of expression level on both FAK, paxillin in the high metastatic cell line. The phosphorylation protein near 125 kDa was increased.
From the above fact, It was shown that high invasion ability, expression increase level of signal transduction molecule such as FAK, paxillin, increase the protein phosphorylation was important so that the cancer cell may acquire metastatic ability to cervical lymph node.

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The relationship between delayed cervical lymph node metastasis and clinico-pathological prognostic factors was retrospectively investigated in 57 patients with NO in squamous cell carcinoma of the to tongue who underwent surgical treatment from 1981 to 1996.
1. Delayed cervical lymph node metastases developed in 11 of 57 patients (19.3%) within 5 years. Factors significantly associated with the development of delayed cervical lymph node metastases were tumor size, tumor thickness, vasucular permeation, and histological grading of malignancy.
2. The incidence of delayed cervical lymph node metastasis increased markedly when the tumor thickness was over 4 mm, the tumor size was over 30 mm, and histological malignancy point was over 17 points.
Thus, these results demonstrated that concervative neck dissection is indicated in patients with N0 in carcinoma of the tongue whose tumors are >30 mm in size, >4 mm in thickness, and >17 points in histological malignancy point.

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To predict indicators for occult neck metastasis, we evaluated clinicopathological findings in N0 cases of squamous tongue carcinoma.
Forty previously untreated patients with biopsy-proved squamous tongue carcinoma, between January 1983 and April 2000, were retrospectively reviewed. All of the patients received a glossectomy alone. Thirty patients did not have a neck dissection at any time, and 10 patients subsequently required a neck dissection, when lymph node metastasis became clinically apparent. These two groups were compared with respect to T-stage, type of growth, tumor thickness, histologic malignant score (by Anneroth, 1987), argyrophilic nucleolar organizer regions (AgNORs) count, and Ki-67 labeling index.
The significant factors for lymph node metastasis were tumor thickness, degree of keratinization, mitosis, pattern of invasion, stage of invasion, and Ki-67 labeling index.
These factors are useful in predicting occult cervical lymph node metastasis.

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Clinical examination of 24 N0 cases of squamous cell carcinoma of the tongue (10 cases), the floor of the mouth (10 cases), and mandibular gingiva (4 cases), which received unilateral supraomohyoid neck dissection, was retrospectively performed.
Pathologically, lymph node metastasis was recognized in 8 cases (33.3%) of which prognoses are good. Among the 16 patients in which pathologically lymph node metastasis was not recognized, 1 patient had died of cervical lymph node metastasis, found after surgery, and the other 15 patients were surviving without recurrence or metastasis.
Three metastatic lymph nodes (LNs) were recognized in 1 case, and 1' LN in 7 cases. LNs were located in level 1 in 6 cases, and in level 2 in 2 cases. An extracapsular metastatic lesion was found in level 1 in 1 case. Histopathological malignancy of the primary lesion was relatively high in most of the cases examined.
From the results, it is suggested that supraomohyoid neck dissection may be effective not only for diagnosis but also for therapy, considering the histopathological malignancy of the primary lesion.

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The conditions under which an elective neck dissection for oral cancer is indicated were determined, with reference to outcomes. We retrospectively reviewed 42 patients who underwent supraomohyoid neck dissection (SOHND), and 52 patients who underwent conservative neck dissection (CND), between 1989 and 1999. Histopathologically positive lymph nodes (pN+) were found in 14.3 % (6 of 32 patients) at SOHND, and in 55.6 % (10 of 18) at CND, in patients with no clinical findings of metastasis (N0) . There was no significant difference in the 5-year survival rates between SOHND and CND patients. In both SOHND and CND cases, however, patients who had responded well to preoperative treatment had better survival rates than other patients. Metastases of level N or V in patients who had N_{1, 2} or pN+ were recognized in mesopharyngeal cancer and oral canner invading the pharyngeal area.
In the cases in which preoperative treatment was effective, SOHND was indicated as the elective neck dissection of choice. Conservative neck dissection should be performed in cases of oral cancer invading the pharyngeal area.

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As malignancy expression of the cancer cell, First, Atypia of tumor cell or tissue polymorphism are strong. Second, the tumor cells were high growth ratio and that it destroys the tissue in the tumor circumference. Third, it is mentioned that the metastasis is formed. For example, increase and heterogeneity of the nuclear chromatin are observed as the matter exchange or reflection of the abnormal interaction between nucleated cell quality, and as the result, the abnormality of the protein synthesis process appears. It tries to make the increase in the nucleolus to be a result of accentuation and much quick turnover of RNA the approach of the cell proliferation. Simultaneously, the mitosis indicates the accentuation when it makes cell proliferation, modulation in cell cycle, and generation of chromosomal abnormality. The cell becomes malignant like this, and by acquiring the proliferation capability, various expressions appear in the cell. In this study, immunohistochemical analysis and genetic analysis of cancer cell were carried out, and various malignancy of the cancer cell was searched.
As the result, it was indicated that to search the phenotype of the malignancy in cell proliferation area of the carcinoma tissue was important.

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Prognostic significance of nuclear DNA content was examined in oral squamous cell carcinoma. Using image cytophotometry, nuclear DNA content of cancer cells in the invasive tumor front was selectively measured in paraffin embeded biopsy tissue from 197 oral squamous cell carcinomas. 4c exceeding rate (4cER) was employed as an interpretation of the DNA histogram. The median 4cER for 197 tumors was 9.7% with range from 0 to 51%. In relation to various clinicopathological factors, high 4cER associated with advanced stage and grade. Five year cause specific survival rate was 75% for the whole series; 90% for patients with less than 9.7% of 4cER and 60% for patients with 9.7% or more. In each subgroup of mode of cancer invasion (Yamamoto-Kohama classification) excepting mode-1 and -2, there was a trend toward enhanced survival rate in low 4cER. This tendency was statistically significance only in mode-3. Furthermore, 4cER was the most powerful prognostic indicator in a multivariate analysis for patients with mode-3.
From these results, it was suggested that 4cER serves as useful prognostic indicator in oral squamous cell carcinoma.

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