Immunohistochemical Analysis of Oral Dysplasia: Diagnostic Assessment by Fascin and Podoplanin Expression

The aim of this study was to investigate fascin and podoplanin expression in oral dysplasia and carcinoma in situ (CIS) immunohistochemically, and to evaluate their relationship to histopathological diagnosis based on architectural and cytological features. Fascin and podoplanin expression patterns were analyzed immunohistologically in 26 specimens of oral lesions, including benign disease (hyperplasia, papilloma, and others), intraepithelial neoplasia/borderline disease (dysplasia), and malignant disease (CIS, invasive squamous cell carcinoma). Fascin expression was scored into four original categories, and podoplanin expression was scored into five previously established categories. The relationship between the immunohistochemically determined scores of fascin and podoplanin expression and the architectural and cytological features in the hematoxylin-eosin-stained slides was analyzed statistically. The immunostaining scores for fascin and podoplanin were significantly higher in dysplasia and CIS than in benign disease (p=0.0011, p=0.00036), and they were significantly higher in dysplasia than in benign disease (p=0.0087, p=0.0032). In all cases of invasive SCC, fascin was expressed mainly in the cytoplasm of the tumor cells and fascin expression extended from the destruction of the basal layer of the epithelium to the upper layer of the epithelium and podoplanin was expressed in the cytoplasm and membrane of the tumor cells. This was the first report of up-regulation of fascin in oral dysplasia. Our results suggest that it would be helpful for improving the diagnostic accuracy of oral dysplasia and CIS to assess the expression of fascin and podoplanin immunohistochemically

Biomarker discovery for practice of precision medicine in hypopharyngeal cancer: a theranostic study on response prediction of the key therapeutic agents

Background: Hypopharyngeal cancer is a relatively rare malignancy with poor prognosis. Current chemotherapeutic algorithm is still far from personalized medicine, and the identification of the truly active therapeutic biomarkers and/or targets is eagerly awaited.Methods: Venturing to focus on the conventional key chemotherapeutic drugs, we identified the most correlative genes (and/or proteins) with cellular sensitivity to docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-FU) in the expression levels, through 3 steps approach: genome-wide screening, confirmation study on the quantified expression levels, and knock-down and transfection analyses of the candidates. The probable action pathways of selected genes were examined by Ingenuity Pathway Analysis using a large-scale database, The Cancer Genome Atlas.Results: The first genome-wide screening study derived 16 highly correlative genes with cellular drug sensitivity in 15 cell lines (|R| > 0.8, P 0.5, P Conclusion: We newly propose 4 molecules -AGR2, PDE4D,NINJ2 and CDC25B) as the powerful exploratory markers for prediction of cellular response to 3 key chemotherapeutic drugs in hypopharyngeal cancers and also suggest their potentials to be the therapeutic targets, which could contribute to the development of precision medicine of the essential chemotherapy in hypopharyngeal patients.</p

Primary tumor-secreted lymphangiogenic factors induce pre-metastatic lymphvascular niche formation at sentinel lymph nodes in oral squamous cell carcinoma

Objectives: The objectives of this study were to evaluate the formation of lymphvascular niches in lymph nodes of patients with oral squamous cell carcinoma (OSCC), and investigate the roles of lymphangiogenic and angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D, expressed in the primary tumors. Materials and Methods: Forty-four patients with previously untreated clinically late T2 or T3 OSCC of cN0 were evaluated for primary tumors and 166 sentinel lymph nodes (SLNs). Primary tumors were immunohistochemically analyzed for expressions of VEGFs. Densities of lymphatic vessels (LVDpodoplanin) and high endothelial venules (HEVD) in the SLNs were also calculated using antibodies for each marker, podoplanin and MECA-79, respectively. Results: In 25 patients, all lymph nodes were metastasis-negative, whereas, in 19 patients, metastasis was positive for at least one lymph node (either at SLN, non-SLN, or nodal recurrence). From the analyses of 140 SLNs without metastasis, LVDpodoplanin in 50 SLNs of metastasis-positive cases was significantly higher than that in 90 SLNs of metastasis-negative cases (p = 0.0025). HEVD was not associated with lymph node metastasis. The patients with VEGF-A-High or VEGF-D-High tumors had significantly higher LVDpodoplanin than patients with their Low counterparts (p = 0.0233 and p = 0.0209, respectively). In cases with lymph node metastasis, the VEGF-D-expression score was significantly higher than in those without lymph node metastasis (p = 0.0006). Conclusions: These results suggest that lymph node lymphangiogenesis occurs before metastasis in OSCC. VEGF-A and VEGF-D play critical roles in this process. VEGF-D is a potential predictive marker of positive lymph node metastasis in cN0 patients. © 2015 Wakisaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Attempting to define sentinel node micrometastasis in oral squamous cell carcinoma

OBJECTIVE:The aim of this supplemental study of a sentinel node (SN) biopsy (SNB) trial for oral squamous cell carcinoma (OSCC) was to assess the effectiveness in identifying micrometastasis and determining whether elective neck dissection (END) is necessary. MATERIALS AND METHODS:Twenty-three patients with pathologically positive SNs were included. The sizes of the metastatic lesions in positive SNs (SMSNs) were classified and the rates of occult metastasis of non-SNs were compared. RESULTS:The patients were divided according to the SMSN:<0.2 mm (group A, n=3);0.2 mm to <2.0 mm (group B, n=7);and ≥2.0 mm (group C, n=13). The rates of occult metastasis in groups A, B, and C were 0% (0/3), 14% (1/7) and 23% (3/13), respectively. CONCLUSION:Rare cancer cell distribution to nodes other than SNs was observed in the patients with SN metastatic lesions of at least smaller than 0.2 mm in size, suggesting the possibility of defining SN micrometastasis in N0 OSCC

Extratemporal Malignant Nerve Sheath Tumor of Facial Nerve with Coexistent Intratemporal Neurofibroma Mimicking Malignant Intratemporal Extension

We present an extremely unusual case of an extratemporal facial nerve malignant peripheral nerve sheath tumor (MPNST) arising from preexistent intratemporal neurofibroma, illustrating a difficulty in discriminating between perineural spread of the MPNST and the preexistent intratemporal neurofibroma on preoperative radiographic images. The most interesting point was that preoperative CT scan and MR images led to misinterpretation that MPNST extended proximally along the facial nerve canal. It is important to recognize that the intratemporal perineural spread of neurofibromas and MPNST share common imaging characteristics. This is the first report (to our knowledge) of these 2 lesions coexisting in the facial nerve, leading to misinterpretation on preoperative images

Primary Small Cell Carcinoma of the Hypopharynx: A Report of Two Cases and Review of Nine Additional Cases

Objective. Two patients with primary small cell carcinoma (SmCC) of the hypopharynx, an extremely rare site for the occurrence of SmCC, are reported and nine additional well-documented cases are reviewed. Methods. Case report and review of the literature concerning primary SmCC of the hypopharynx. Results. On the final analysis, we reviewed eleven cases of primary SmCC of the hypopharynx. The tumors contained mixed elements of SmCC and squamous cell carcinoma (SCC) in six (55%) of eleven patients. Out of eleven patients, two patients had distant metastasis at the initial presentation. Even though nine patients presented with locoregional disease, development of distant metastasis after treatment was seen in five patients (56%), whereas there was no report of treatment failure on the primary site. To achieve more than two-year survival, patients should have received more than 4 cycles of chemotherapy. Conclusion. We report two cases of primary SmCC of the hypopharynx with a review of the literature. In more than half of the cases, combined carcinomas with SCC are seen. Because this tumor has a strong propensity for distant metastasis even in patients with clinically localized tumor, new powerful systemic agents should be explored