Purpose: Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. Mucoepidermoid carcinoma translocated gene 1-mastermind-like gene family (MECT1-MAML2) gene fusion was identified from a recurring t(11;19)(q21;p13) translocation, which is often the sole cytogenetic alteration in this disease. This fusion transcript has been frequently detected in mucoepidermoid carcinoma and shown to be involved in the transformation of epithelial cells. However, its clinicopathologic significance remains unclear. Experimental Design: Seventy-one cases of mucoepidermoid carcinoma and 51 cases of nonmucoepidermoid carcinoma salivary gland tumors (including 26 Warthin tumor cases) were retrospectively analyzed. RNAwas extracted from archival materials: histologic paraffin specimens in all cases and cytologic specimens in10 mucoepidermoid carcinoma cases.The MECT1-MAML2 fusion transcript was detected by a reverse transcription-PCR assay, which can be applied to both histologic and cytologic specimens. The presence of the fusion transcript was correlated with relevant clinicopathologic and survival data of the mucoepidermoid carcinoma patients. Results:The MECT1-MAML2 fusion transcript was detected in 27 of the 71 (38%) mucoepidermoid carcinoma cases but not in any case of nonmucoepidermoid carcinoma tumors. The reverse transcription-PCR results showed no difference between histologic and cytologic specimens. Detection of the MECT1-MAML2 fusion transcript was associated with a less advanced clinical stage and a low-grade tumor histology.The presence of the transcript was associated with longer disease-free and overall survivals on univariate analysis and emerged as an independent prognostic factor for longer overall survival on multivariate analysis. Conclusions: The MECT1-MAML2 fusion transcript may be specific to mucoepidermoid carcinoma and associated with a distinct mucoepidermoid carcinoma subset that exhibits favorable clinicopathologic features and an indolent clinical course.

Wnt5a is a representative ligand that activates the b-catenin-independent pathway in Wnt signaling. Although it has been reported that abnormal activation of the Wnt/ b-catenin-dependent pathway is often observed in human prostate cancer, the involvement of the b-catenin-independent pathway in this cancer is unclear. Abnormal expression of Wnt5a and b-catenin was observed in 27 (28%) and 49 (50%) of 98 prostate cancer cases, respectively, by immunohistochemical analyses. Simultaneous expression of Wnt5a and b-catenin was observed in only five cases, suggesting their exclusive expression. The positive detection of Wnt5a was correlated with high Gleason scores and biochemical relapse of prostate cancer, but that of b-catenin was not. Knockdown and overexpression of Wnt5a in human prostate cancer cell lines reduced and stimulated, respectively, their invasion activities, and the invasion activity required Frizzled2 and Ror2 as Wnt receptors. Wnt5a activated Jun-N-terminal kinase through protein kinase D (PKD) and the inhibition of PKD suppressed Wnt5a-dependent cell migration and invasion. In addition, Wnt5a induced the expression of metalloproteinase-1 through the recruitment of JunD to its promoter region. These results suggest that Wnt5a promotes the aggressiveness of prostate cancer and that its expression is involved in relapse after prostatectomy.

Background Many histopathologic parameters in head and neck squamous cell carcinoma have been identified as predictive factors for cervical metastasis. Several studies focused on tumor thickness, and the depth of invasion was suggested to have a relationship to the occurrence of cervical metastasis. Nonetheless, the criterium for elective neck therapy in terms of tumor depth is still inconclusive. Therefore, a retrospective study was undertaken to substantiate the differing results in the literature with our own findings concerning the interrelationship between tumor thickness and clinically suspicious neck, as well as occult neck disease. In addition, the study attempted to identify further predictive factors for cervical metastasis in squamous cell carcinoma of the tongue. Methods The medical records of 34 primarily tongue carcinomas operated without any preoperative therapy between 1980 and 1991 were reviewed. Each patient's tumor type, tumor location, tumor size, invasion mode, depth of invasion, intralymphatic tumor emboli, and perineural invasion were evaluated. Chi‐square contingency tables were used to correlate clinical or histopathologic parameters with metasis in the neck. Results The overall cervical metastasic rate was 35.3% (n = 12/34). In univariate analysis, invasion mode and depth of invasion were statistically significant predictors of regional metastasis at p = 0.0019 and p = 0.0003, respectively. In the group in which tumor depth exceeded 5 mm, the metastatic rate was 64.7% (11/17). In contrast, when the depth of invasion was less than 5 mm, the incidence of cervical metastasis was 5.9% (1/17). Clinically negative necks turned out pathologically positive in 30.0% (n = 9/30). The tumor depth exceeded 5 mm in 43.4% (13/30) of the N0 necks. In the conversion (N0 → N1) group, tumor depth exceeding 5 mm was noted in 88.9% (n = 8/9). Conclusions We suggest that there is a discerning point at 5 mm of tumor depth at which cervical metastasis is probable. Electric neck therapy (surgery or irradiation) is strongly indicated for tumors exceeding 5 mm invasion. Tumor invasion mode and tumor size also bear an impact on the indication for therapy. © 1997 John Wiley & Sons, Inc. Head Neck 19: 205–210, 1997.

This paper proposes an algorithm to estimate human intentions related with walking in order to comfortably and safely support a paraplegia patient's walk. A robot suit "HAL" has been developed for an enhancement of healthy person's activities and for support of physically challenged person's daily life. Assisting method based on bioelectrical signals such as myoelectricity successfully supports healthy person's walking. These bioelectrical signals, however, cannot be measured properly from a paraplegia patient. Therefore another interface that can estimate patients' intentions without any manual controller are desired for robot control since a manual controller deprives a patient of his/her hands' freedom. Estimation of patients' intentions contributes to support not only comfortably but also safely, because an inconformity between the robot suit motion and the patient motion results in his/her stumbling or falling. The proposed algorithm, therefore, estimates patient's intentions from a floor reaction force reflecting patient's weight shift during walking and standing. The effectiveness of this algorithm is investigated through experiments on a paraplegia patient who has a sensory paralysis on both legs, especially his left leg. We show that HAL supports patient's walk properly, estimating his intentions based on floor reaction force.

Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. We and others showed that CRTC1-MAML2 gene fusion was associated with favorable clinicopathological tumor features. Recently, a novel gene fusion, CRTC3-MAML2, was reported as a rare gene alteration in a case of mucoepidermoid carcinoma. However, its frequency and clinicopathological significance remains unclear. In all, 101 cases of mucoepidermoid carcinoma and 89 cases of non-mucoepidermoid carcinoma of the salivary gland were analyzed, and RNA was extracted from formalin-fixed, paraffin-embedded specimens. In the CRTC family, there have been three genes, CRTC1, CRTC2, and CRTC3. We developed reverse transcriptionpolymerase chain reaction (RT-PCR) assays for CRTC1-MAML2, CRTC2-MAML2, and CRTC3-MAML2 fusions. Clinicopathological data of the patients were obtained from their clinical records. Of 101 cases of mucoepidermoid carcinoma, 34 (34%) and 6 (6%) were positive for CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts. However, in the 89 cases of non-mucoepidermoid carcinoma, neither transcript was noted. In the former cases, CRTC1-MAML2 and CRTC3-MAML2 fusions were mutually exclusive. The other fusion, CRTC2-MAML2, was not detected. We confirmed that the clinicopathological features of CRTC1-MAML2-positive mucoepidermoid carcinomas indicated an indolent course. CRTC3-MAML2-positive mucoepidermoid carcinomas also had clinicopathologically favorable features; all cases showed a less advanced clinical stage, negative nodal metastasis, no high-grade tumor histology, and no recurrence or tumor-related death after surgical resection of the tumor. It is interesting to note that patients with CRTC3-MAML2-positive tumors (mean 36 years of age) were significantly younger that those with the CRTC1-MAML2 fusion (55 years) and those with fusionnegative tumors (58 years). In conclusion, CRTC3-MAML2 fusion, which is mutually exclusive with CRTC1-MAML2 fusion and specific to mucoepidermoid carcinoma, may be detected more frequently than previously expected. Mucoepidermoid carcinomas possessing CRTC3-MAML2 fusion may be associated with favorable clinicopathological features and patients may be younger than those with CRTC1-MAML2 fusion or those with no detectable gene fusion. Keywords: mucoepidermoid carcinoma; CRTC3-MAML2 fusion; clinicopathological study; prognosis Mucoepidermoid carcinoma, representing 5% of all salivary gland tumors and 20% of the malignant forms, is the most frequent primary malignancy of the salivary gland in both adults and children.

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PURPOSE This study aimed to compare patients with early oral cavity squamous cell carcinoma (OCSCC) (tumor category [T] 1-2, node-negative, and no distant metastasis) treated with traditional elective neck dissection (ND) with those managed by sentinel lymph node biopsy (SLNB) using survival and neck function and complications as end points. METHODS Sixteen institutions in Japan participated in the study (trial registration number: UMIN000006510). Patients of age ≥ 18 years with histologically confirmed, previously untreated OCSCC (Union for International Cancer Control TNM Classification of Malignant Tumors 7th edition T1-2, node-negative no distant metastasis), with ≥ 4 mm (T1) depth of invasion, were randomly assigned to undergo standard selective ND (ND group; n = 137) or SLNB-navigated ND (SLNB group; n = 134). The primary end point was the 3-year overall survival rate, with a 12% noninferiority margin; secondary end points included postoperative neck functionality and complications and 3-year disease-free survival. Sentinel lymph nodes underwent intraoperative multislice frozen section analyses for the diagnosis. Patients with positive sentinel lymph nodes underwent either one-stage or second-look ND. RESULTS Pathologic metastasis-positive nodes were observed in 24.8% (34 of 137) and 33.6% (46 of 134) of patients in the ND and SLNB groups, respectively ( P = .190). The 3-year overall survival in the SLNB group (87.9%; lower limit of one-sided 95% CI, 82.4) was noninferior to that in the ND group (86.6%; lower limit 95% CI, 80.9; P for noninferiority < .001). The 3-year disease-free survival rate was 78.7% (lower limit 95% CI, 72.1) and 81.3% (75.0) in the SLNB and ND groups, respectively ( P for noninferiority < .001). The scores of neck functionality in the SLNB group were significantly better than those in the ND group. CONCLUSION SLNB-navigated ND may replace elective ND without a survival disadvantage and reduce postoperative neck disability in patients with early-stage OCSCC.

Septins are a family of conserved cytoskeletal GTPases implicated in a variety of cellular functions such as cytokinesis and vesicle trafficking. Here, we report identification of an yet uncharacterized septin, Sept11, in septin complexes purified from porcine brain. The transcripts were detected in all tested tissues except leukocytes. A Sept11 mutant with apparently reduced GTPase activity did not form filaments in the transient expression system using COS7 cells. By Western blot analysis using a specific antibody, Sept11 was detected in various cell lines as well as brain tissues. Septin complexes immunoisolated from porcine brain with anti-Sept9 and anti-Sept11 antibodies were found to contain different Sept9 isoforms based on SDS-PAGE analyses followed by silver-staining and Western blotting. Immunofluorescent study revealed cell type-dependent intracellular localization of the protein; Sept11 was colocalized dominantly with microtubules and actin stress fibers in HMEC cells and REF52 cells, respectively, and their filamentous distribution was dependent on the cytoskeleton structures with which the protein is colocalized. Sept11 partially colocalized with stress fibers and microtubules in HeLa cells.