Bone-patellar tendon-bone autograft maturation is superior to double-bundle hamstring tendon autograft maturation following anatomical anterior cruciate ligament reconstruction.

PURPOSE: The primary purpose of this study was to evaluate the second-look arthroscopic findings 1 year postoperatively and magnetic resonance imaging (MRI) findings 2 years after anterior cruciate ligament reconstruction (ACLR) using bone-patellar tendon-bone autograft (BTB) or hamstring tendon autograft (HT). Secondary purpose included clinical results from physical examination, including range of motion, Lachman test, pivot shift test, and knee anterior laxity evaluation, and the clinical score for subjective evaluations at 2 years after surgery. METHODS: Between 2015 and 2018, 75 patients with primary ACL injuries were divided into either the BTB group (n = 30) or HT group (n = 45). When using HT, an anatomical double-bundle ACLR was performed. BTB was indicated for athletes with sufficient motivation to return to sporting activity. Graft maturation on second-look arthroscopy was scored in terms of synovial coverage and revascularization. All participants underwent postoperative MRI evaluation 2 years postoperatively. The signal intensity (SI) characteristics of the reconstructed graft were evaluated using oblique axial proton density-weighted MR imaging (PDWI) perpendicular to the grafts. The signal/noise quotient (SNQ) was calculated to quantitatively determine the normalized SI. For clinical evaluation, the Lachman test, pivot shift test, KT-2000 evaluation, Lysholm score, and Knee injury and Osteoarthritis Outcome Score (KOOS) were used. RESULTS: Arthroscopic findings showed that the graft maturation score in the BTB group (3.6 ± 0.7) was significantly greater than that in the anteromedial bundle (AMB; 2.9 ± 0.2, p = 0.02) and posterolateral bundle (PLB; 2.0 ± 0.9, p = 0.001) in the HT group. The mean MRI-SNQs were as follows: BTB, 2.3 ± 0.5; AMB, 2.9 ± 0.9; and PLB, 4.1 ± 1.1. There were significant differences between BTB, AMB, and PLB (BTB and AMB: p = 0.04, BTB and PLB: p = 0.003, AMB and PLB: p = 0.03). Second-look arthroscopic maturation score and MRI-SNQ value significantly correlated for BTB, AMB, and PLB. No significant differences were detected in clinical scores. There was a significant difference (p = 0.02) in the knee laxity evaluation (BTB: 0.9 ± 1.1 mm; HT: 2.0 ± 1.9 mm). CONCLUSION: BTB maturation is superior to that of double-bundle HT based on morphological and MRI evaluations following anatomical ACLR, although no significant differences were found in clinical scores. Regarding clinical relevance, the advantages of BTB may help clinicians decide on using the autograft option for athletes with higher motivation to return to sporting activity because significant differences were observed in morphological evaluation, MRI assessment, and knee anterior laxity evaluation between BTB and double-bundle HT. LEVEL OF EVIDENCE: Level IV.

Femoral nerve versus adductor canal block for early postoperative pain control and knee function after anterior cruciate ligament reconstruction with hamstring autografts: a prospective single-blind randomised controlled trial.

INTRODUCTION: The optimal pain management strategy for postoperative pain after anterior cruciate ligament reconstruction (ACLR) remains unclear. This study compared femoral nerve block (FNB) and adductor canal block (ACB) for pain management of early postoperative pain, knee function, and recovery of activity of daily living (ADL) after ACLR using hamstring autografts. MATERIAL AND METHODS: In this prospective, single-blind, randomised controlled trial, 64 patients aged 12-56 years who underwent anatomical double-bundle ACLR with a hamstring autograft between August 2019 and May 2020 were randomised to undergo preoperative FNB (n = 32) or ACB (n = 32). The peripheral nerve block was performed by a single experienced anaesthesiologist under ultrasound guidance. The primary outcomes were postoperative pain as evaluated using the visual analogue scale (VAS) at 3, 6, 12, 24, and 48 h postoperatively and the need for pain relief. The secondary outcome was knee function, including the recovery of range of motion, contraction of the vastus medialis, and stable walking with a double-crutch (ADL), as evaluated by blinded physical therapists. RESULTS: There were no significant differences in patient demographics between the two groups. The VAS scores, need for pain relief, knee function, and ADL did not significantly differ between the groups. CONCLUSION: FNB and ACB provided comparable outcomes related to early postoperative pain, knee function, and ADL after double-bundle ACLR using hamstring autografts. Further research is necessary to evaluate the mid- to long-term effect of each block on recovery of knee function and ADL. LEVEL OF EVIDENCE: I.

Joint effusion at 6 months is a significant predictor of joint effusion 1 year after anterior cruciate ligament reconstruction.

PURPOSE: This study aimed to assess the risk factors for prolonged joint effusion in patients undergoing double-bundle anterior cruciate ligament reconstruction (ACLR). METHODS: In total, 160 patients who underwent primary ACLR using autograft hamstring between 2015 and 2018 were retrospectively reviewed. Joint effusion was defined as any grade ≥ 2 (range, 0-3) according to the MRI Osteoarthritis Knee Score (MOAKS). Univariate and multivariate logistic regression analyses were performed. RESULTS: The median age of the patients was 25 years (range 14-68 years) at the time of the surgery; there were 89 women and 71 men. At 1 year, 46 (28.8%) patients experienced knee joint effusion, as defined by the MOAKS. Univariate analysis revealed that age, preoperative Kellgren-Lawrence (K-L) grade, and joint effusion at 6 months were significantly associated with joint effusion at 1 year. In the multivariate analysis, joint effusion at 6 months was significantly associated with joint effusion at 1 year (odds ratio, 68.0; 95% confidence interval, 22.1-209.4). No significant difference in the Lysholm scores was observed between patients with and without joint effusion at 1 year (n.s.). CONCLUSIONS: Joint effusion at 6 months was significantly associated with joint effusion 1 year after ACLR. LEVEL OF EVIDENCE: III.

Surgical Management of Median Cleft Lip Extending as Far as Alveolus Using Bone Grafting.

Median clefts, which run through the midline of the upper lip, and alveolus are considered a type of craniofacial cleft. A Tessier number 0 median cleft lip is the rarest, and there are few reports concerning its surgical management. Here, we describe the case of a 6-year-old boy who presented at our hospital with a median cleft and alveolus of the upper lip with a shortened bifid frenulum. Inverted-V and Z-plasty incisions were performed for the median cleft and iliac bone grafting for the midline alveolus. At 1 year 5 months later, the postoperative course was uneventful, and proper approximation of the orbicularis oris muscle and vermilion were achieved, with a symmetrical Cupid's bow and labial tubercle and philtrum.

Morphologic Evaluation for Safe Le Fort I Osteotomy in Cleft Lip and Palate.

OBJECTIVE: The present study aimed to determine the structure and morphology of the maxilla in patients with cleft lip and palate to ensure safe Le Fort I osteotomy. PATIENTS: A total of 34 sides of 17 patients with unilateral cleft lip and palate (nonsyndromic cases) were included in this study. The control group included 10 sides of 5 patients who exhibited skeletal mandibular protrusion without malformation. METHODS: Finite element analysis was performed to examine the distribution of occlusal force over the maxilla, and continuous 3-dimensional measurement was performed at the sites of stress concentration. RESULTS: In patients with cleft lip and palate, bones at the lateral border of the piriform aperture and the anterior wall of the maxillary sinus were significantly thicker than those in controls ( P < .05). Furthermore, the attachment of the pterygomaxillary junction was wider and thicker ( P < .05), and the anterior distance to the descending palatine artery was shorter ( P < .01) in patients with cleft lip and palate than in controls. Our results further indicated that alveolar bone grafting may significantly influence bone thickness and the attachment state of the pterygomaxillary junction. CONCLUSIONS: Our results suggest that the complications of LFI can be reduced in patients with cleft lip and palate by ensuring proper understanding of each patient's maxillary anatomy and bone thickness, as well as the location of the descending palatine artery and the attachment state of the pterygomaxillary junction.

Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa.

The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells.

A case of chondrosarcoma arising in the temporomandibular joint.

Chondrosarcoma is a malignant tumor originating in cartilaginous cells. And there are only few reports of the case of chondrosarcoma in temporomandibular joint. We discuss a case of chondrosarcoma in temporomandibular joint in a 28-year-old man. Tumor was in contact with the dura, but en bloc resection was performed. After surgical resection of the tumor, face defect was reconstructed by rectus abdominis-free flap. And there is no recurrence after ten years from the resection.

A histologic study of deformation of the mandibular condyle caused by distraction in a rat model.

OBJECTIVE: This study investigated the bone resorption process of the rat mandibular condyle after mandibular distraction. STUDY DESIGN: Male Wistar rats at 10 weeks of age underwent unilateral mandibular distraction at 0.175 mm per 12 hours for 10 days. Histologic and histochemical analyses were performed at postoperative day 1 and weeks 1 and 3. RESULTS: High-resolution computed tomography (micro-CT) observations showed that deformation of the condyle occurred in the anterior region, where a discontinuity of the condylar cartilage layer was found in histologic sections. This destroyed area gathered many osteoclasts. In the central region, disorganization with a thin hypertrophic cell layer was recognizable by day 1 but later thickened. Morphologic recovery of the mandibular condyle could be attained by week 3 in this animal model. CONCLUSIONS: These morphologic findings indicate that rapid deformation of the condyle, with destruction of the cartilage layer and bone resorption, was caused by artificial distraction.

Autotransplantation or replantation of cryopreserved teeth: a case series and literature review.

BACKGROUND: The aim of this report was to evaluate the outcome of autotransplantation or replantation of cryopreserved teeth clinically and radiographically. Donor teeth were slowly frozen in a controlled-rate freezer using 5% dimethylsulfoxide (DMSO) and 6% hydroxyethyl starch (HES) as protectants. Seven cryopreserved teeth, with duration of storage ranging from 4 to 36 months, were autotransplanted or replanted at Niigata University Medical and Dental Hospital. Endodontic treatment involving root canal debridement followed by interim root canal filling with calcium hydroxide was started 3 weeks after the operation and continued with replacement of the calcium hydroxide filling at 2-week to 3-month intervals. Three transplants showed periodontal regeneration clinically and radiographically, whereas replacement root resorption was observed in the remaining transplants. From the results, it can be concluded that cryopreserved tooth autotransplantation has potential for clinical use; however, the risk of replacement root resorption remains.

Histochemical aspects of the vascular invasion at the erosion zone of the epiphyseal cartilage in MMP-9-deficient mice.

We have histologically examined vascular invasion and calcification of the hypertrophic zone during endochondral ossification in matrix metalloproteinase (MMP)-9 deficient (MMP-9-/-) mice and in their littermates at 3 days, 3 weeks and 6 weeks after birth. Capillaries and osteoclasts at the chondro-osseous junction showed an intense MMP-9 immunopositivity, suggesting that they recognize chemical properties of cartilaginous matrices, and then release MMP-9 for cartilage degradation. CD31-positive capillaries and tartrate-resistant acid phosphatase-reactive osteoclasts could be found in the close proximity in the region of chondro-osseous junction in MMP-9-/- mice, while in wild-type mice, vascular invasion preceded osteoclastic migration into the epiphyseal cartilage. Although MMP-9-/- mice revealed larger hypertrophic zones, the index of calcified area was significantly smaller in MMP-9-/- mice. Interestingly, the lower layer of the MMP-9-/- hypertrophic zone showed intense MMP-13 staining, which could not be observed in wild-type mice. This indicates that MMP-13 may compensate for MMP-9 deficiency at that specific region, but not to a point at which the deficiency could be completely rescued. In conclusion, it seems that MMP-9 is the optimal enzyme for cartilage degradation during endochondral ossification by controlling vascular invasion and subsequent osteoclastic migration.

Changes in overnight arterial oxygen saturation after mandibular setback.

Mandibular setback reduces space in the pharyngeal airway, and it has been suggested that it might induce sleep-disordered breathing. We report on its effects on space in the pharyngeal airway and respiratory function during sleep. We studied 78 patients (29 men and 49 women) in whom skeletal class III malocclusions had been corrected. The mean (range) age at operation was 24 (16-38) years and body mass index (BMI) 21.4 (16.1-30 .9)kg/m(2). Morphological changes were evaluated on lateral cephalograms taken three times: preoperatively, a few days postoperatively, and more than 6 months postoperatively. Overnight arterial oxygen saturation (SpO2) was measured by pulse oximetry 6 times: preoperatively, and on days 1, 3, 5, and 7, and 6 months postoperatively; oximetric indices were calculated. Those immediately after mandibular setback were significantly worse than those preoperatively, although they gradually improved. There were positive correlations between BMI and oximetric indices, and little association between changes in mandibular position and oximetric indices. There was no evidence of sleep-disordered breathing 6 months after mandibular setback because most patients adapt to the new environment for respiratory function during sleep. However, some (particularly obese) patients may develop sleep-disordered breathing just after mandibular setback. In such patients attention should be paid to respiratory function during sleep in the immediate postoperative period, and careful postoperative follow-up is needed.

Distinct expression patterns and roles of aldehyde dehydrogenases in normal oral mucosa keratinocytes: differential inhibitory effects of a pharmacological inhibitor and RNAi-mediated knockdown on cellular phenotype and epithelial morphology.

Aldehyde dehydrogenases (ALDHs), enzymes responsible for detoxification and retinoic acid biosynthesis, are considered a potent functional stem cell marker of normal and malignant cells in many tissues. To date, however, there are no available data on ALDH distributions and functions in oral mucosa. This study aims to clarify the levels and types of ALDH expression using immunohistochemistry with accompanying mRNA expression as well as an ALDEFLUOR assay, and to assess phenotypic and histological changes after manipulation of the ALDH activity of oral keratinocytes to increase the potency of a tissue-engineered oral mucosa by a specific ALDH inhibitor, diethylaminobenzaldehyde (DEAB), together with small interfering RNA of ALDH1A3 and ALDH3A1. Results showed the mRNA and cytoplasmic protein expression of ALDH1A3 and ALDH3A1 to be mostly localized in the upper suprabasal layer although no ALDH1A1 immunoreaction was detected throughout the epithelium. Oral keratinocytes with high ALDH activity exhibited a profile of differentiating cells. By pharmacological inhibition, the phenotypic analysis revealed the proliferating cell-population shifting to a more quiescent state compared with untreated cells. Furthermore, a well-structured epithelial layer showing a normal differentiation pattern and a decrease in Ki-67 immunopositive basal cells was developed by DEAB incubation, suggesting a slower turnover rate efficient to maintain undifferentiated cells. Histological findings of a regenerated oral epithelium by ALDH1A3 siRNA were similar to those when treated with DEAB while ALDH3A1 siRNA eradicated the epithelial regenerative capacity. These observations suggest the effects of phenotypic and morphological alterations by DEAB on oral keratinocytes are mainly consequent to the inhibition of ALDH1A3 activity.

Effects of intermittent parathyroid hormone treatment on new bone formation during distraction osteogenesis in the rat mandible.

OBJECTIVE: The effect of intermittent parathyroid hormone (PTH[1-34]) treatment on bone regeneration in a rat model of mandibular distraction was evaluated using microcomputed tomography. STUDY DESIGN: After a 5-day latency period, mandibles of 18 rats were distracted at 0.2 mm/12 hours for 10 days, and rats in the PTH and control groups received subcutaneous injections of PTH(1-34) at a dosage of 60 µg/kg body weight or a vehicle only, respectively, 3 times a week. The animals were humanely killed after 10 days of distraction and after 1 week and 3 weeks of consolidation. RESULTS: In reconstructed 3-dimensional images of the distracted mandible, mean bone volumes of the desired region of interest in the PTH group were significantly larger than those in the control group at all time points. CONCLUSIONS: Intermittent PTH(1-34) treatment enhances new bone formation during mandibular distraction in a rat model, and it may be effective for shortening the consolidation period.

Keratin 10-positive orthokeratotic dysplasia: a new leucoplakia-type precancerous entity of the oral mucosa.

AIMS: We investigated a group of oral mucosal lesions with characteristic hyperorthokeratotic foci, which we termed orthokeratotic dysplasia (OKD), to determine if it could be identified as a distinct histopathological entity. METHODS AND RESULTS: We screened 282 surgical specimens from 200 patients with oral leucoplakia-type squamous cell carcinoma (SCC) or carcinoma in situ (CIS). OKD was defined as an oral mucosal lesional focus in which hyperorthokeratosis was predominant in the presence of the granular cell layer. A total of 84 OKD foci from 62 cases found among the 200 SCC/CIS cases were analysed. According to its rete ridge shapes, OKD was classified into three subtypes: flat (14.3%), leg (63.1%) and intermediate (22.6%). Eighty per cent of OKD foci were adjacent to the main foci of SCC or CIS, and they were demarcated sharply from each other. Most of the OKD constituent cells were immunopositive for keratin 10, but not for keratins 13, 17 or 19. Numbers of Ki-67-positive cells in the first basal layer were greater in OKD than in normal epithelia. CONCLUSIONS: The findings indicate that OKD is a distinct variant of epithelial dysplasia related to malignancies, and hence that it is important to recognize its existence.

Prognostic factors for autotransplantation of teeth with complete root formation.

OBJECTIVES: The aim of the present study was to evaluate the factors affecting the prognosis of the autotransplantation of teeth with complete root formation. STUDY DESIGN: A total of 259 transplanted teeth were studied. The significance of each of the prognostic factors was examined in 2 ways, first in a univariate analysis and then in a multivariate analysis. The comprehensive risk combining these factors that remained after multivariate analysis was calculated. RESULTS: Among 259 transplanted teeth, 27 (10.4%) were judged as unsuccessful cases. In the multivariate analysis, history of root canal treatment of donor tooth, multirooted, maxillary tooth as a donor, and duration of tooth absence at recipient site remained significantly associated with unsuccessful transplantation. Multifarious combination of the significant prognostic factors can decrease the comprehensive risk. CONCLUSIONS: Minimizing the comprehensive risk by combining significant prognostic factors improved the prognosis of autotransplantation of teeth with complete root formation.

Intraepithelially entrapped blood vessels in oral carcinoma in-situ.

It can be difficult to make a certain diagnosis in case of an oral borderline malignant lesion on hematoxylin-eosin-stained sections only. Furthermore, assessment of surgical margins of borderline lesions is difficult with the naked eye. We set out to determine the topographical distribution of capillary blood vessels within the epithelial zone and to assess its use as an aid for histopathological diagnosis and a framework for clinical assessment of lesional margins using optical techniques, such as narrow-band imaging (NBI) endoscopy. Capillary blood vessels entrapped in the epithelial compartment, which we have designated as intraepithelially entrapped blood vessels (IEBVs), were examined for their frequency, location, and shape in normal mucosa, dysplasia, and carcinoma in-situ (CIS) of the tongue using immunohistochemistry for CD31 and type IV collagen. When counted per unit length of epithelial surface, IEBVs increased in number significantly in CIS (5.6 ± 2.8), which was two times more than in normal (1.9 ± 1.6) and dysplastic (2.4 ± 1.5) epithelia. In addition, IEBVs in CIS had compressed shapes with occasional obstruction or collapse with hemorrhage and were arranged perpendicular to and extending up to the epithelial surface. These characteristic IEBVs in CIS were considered to be generated by complex expansion of rete ridges due to carcinoma cell proliferation within the limited epithelial space determined by the basement membrane. The recognition of IEBVs was helpful in the differential diagnosis of oral CIS, and the present data provide a valuable frame of reference for detecting oral CIS areas using such NBI-based optical devices.

Keratinocytes of tissue-engineered human oral mucosa promote re-epithelialization after intraoral grafting in athymic mice.

PURPOSE: The objective of this study was to investigate the role of grafted oral keratinocytes in a transplanted ex vivo-produced oral mucosa equivalent (EVPOME) in the regeneration and/or healing process of the oral mucosa at the recipient site. MATERIALS AND METHODS: The EVPOME was developed in a serum-free defined culture system without a feeder layer. EVPOME is composed of a stratified layer of human oral keratinocytes that are seeded onto a human cadaveric dermis, AlloDerm (LifeCell, Branchburg, NJ). Intraorally grafted EVPOMEs in athymic mice (BALB/c) were excised, contiguous with the surrounding oral mucosa, on days 5, 7, 14, and 21 after grafting. Serial sections were stained with hematoxylin-eosin and immunohistochemically analyzed for cytokeratin 17 (CK17) expression to distinguish the human-cultured EVPOME epithelial keratinocytes from murine oral keratinocytes. RESULTS: All EVPOME epithelial cells showed intense immunoreactivity for CK17, whereas mouse buccal mucosal epithelial cells did not show CK17 immunoreactivity. The grafted EVPOME maintained a stratified epithelial layer for up to 5 days after grafting. By day 7 after grafting, a portion of the EVPOME epithelial layer peeled away from the AlloDerm, and a thin, CK17-immunonegative epithelial layer extended from the adjacent thick epithelial layer of the mouse and contacted the CK17-immunopositive EVPOME epithelium. From days 14 to 21 after grafting, the stratification of the CK17-immunonegative continuous mouse epithelium increased compared with earlier time points and showed a similar appearance to the epithelium of the adjacent mouse mucosa. In contrast, no epithelial coverage of the AlloDerm that was grafted without keratinocytes was observed for up to 21 days after grafting. The grafted AlloDerm without cells resulted in tissue necrosis that was accompanied by a dramatic infiltration of inflammatory cells by day 14. CONCLUSIONS: These findings suggest that grafting of EVPOME with viable oral keratinocytes onto an intraoral mucosal wound plays an active role in promotion of re-epithelialization of the oral wound during the subsequent healing process.

Progressive condylar resorption after mandibular advancement.

Progressive condylar resorption is an irreversible complication and a factor in the development of late skeletal relapse after orthognathic surgery. We have evaluated cephalometric characteristics, signs and symptoms in the temporomandibular joint (TMJ), and surgical factors in six patients (one man and five women) who developed it after orthognathic surgery. The findings in preoperative cephalograms indicated that the patients had clockwise rotation of the mandible and retrognathism because of a small SNB angle, a wide mandibular plane angle, and a "minus" value for inclination of the ramus. There were erosions or deformities of the condyles, or both, on three-dimensional computed tomography (CT) taken before treatment. The mean (SD) anterior movement of the mandible at operation was 12.1 (3.9)mm and the mean relapse was -6.4 (2.5)mm. The mean change in posterior facial height was 4.5 (2.1)mm at operation and the mean relapse was -5.3 (1.8)mm. Two patients had click, or pain, or both, preoperatively. The click disappeared in one patient postoperatively, but one of the patients who had been symptom-free developed crepitus postoperatively. In the classified resorption pattern, posterior-superior bone loss was seen in three cases, anterior-superior bone loss in two, and superior bone loss in one. Progressive condylar resorption after orthognathic surgery is multifactorial, and some of the risk factors are inter-related. Patients with clockwise rotation of the mandible and retrognathism in preoperative cephalograms; erosion, or deformity of the condyle, or both, on preoperative CT; and wide mandibular advancement and counterclockwise rotation of the mandibular proximal segment at operation, seemed to be at risk. The mandible should therefore be advanced only when the condyles are stable on radiographs, and careful attention should be paid to postoperative mechanical loading on the TMJ in high-risk patients.

Enhanced expression of podoplanin in oral carcinomas in situ and squamous cell carcinomas.

OBJECTIVE: Podoplanin, a known lymphatic endothelial cell marker, has been reported to be expressed in various types of cancer. To elucidate the expression of podoplanin in precancerous lesions, we examined the immunohistochemical profiles of podoplanin in oral squamous epithelial lesions. METHOD: We studied a total of 298 foci of squamous cell carcinoma (SCC), carcinoma in situ (CIS), epithelial dysplasia, and hyperplastic and/or normal epithelial lesions by immunohistochemistry using D2-40. RESULTS: There was no positivity for podoplanin in normal or hyperplastic epithelia, while all of the CIS and SCC foci stained positive. Approximately one third of the mild dysplasia foci (10 of 36 foci, 28%) and 80% of moderate dysplasia foci (78/98) showed grade 1 positive reactions (positive only in the 1st layer). Grade 2 reactions (up to 4th layer) were seen in 4 of 98 moderate dysplasia foci (4%), 29 of 74 CIS foci (39%), and 3 of 30 SCC foci (10%). Grade 3 reactions (to more than 5th layer) were found in 35 (47%) CIS foci and 26 (87%) SCC foci. CONCLUSIONS: The relationship between the present histological categorization and podoplanin grade was statistically significant. D2-40 expression is considered to be related to the severity of oral precancerous lesions.

Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ.

To evaluate differential expressions for keratin (K) subtypes 13 and 17 in oral borderline malignancies, we examined 67 surgical specimens of the oral mucosa for their immunohistochemical profiles. From those specimens, 173 foci of epithelial dysplasia, 152 foci of carcinoma in situ (CIS), and 82 foci of squamous cell carcinoma (SCC) were selected according to our diagnostic criteria, along with 20 areas of normal epithelia. In normal epithelia, there was no K17 positivity (0%), whereas definite K13 positivity (100%) was observed. The same tendencies were obtained in mild (undefined) and moderate (true) epithelial dysplasias (K17: 0%; K13: 100%). In contrast, all CIS (100%) had K17 positivities, while K13 positivities were lost in many of them (7%). Similar tendencies were confirmed in invasive SCC (K17: 100%, K13: 4%). Simultaneous immunopositivities for K17 and K13 were found only in SCC (7%) and CIS (4%) foci with distinct keratinization. These foci also showed K10 positivities, though K10 positive areas were not identical to K13 positive areas. The results indicate that expressions of K17 and K13 are reciprocal in oral epithelial lesions and that the K17 emergence is related to malignancies.