Silencing of heat shock factor 1 (HSF1) inhibits proliferation, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma is characterized by high rates of morbidity and mortality. Evidence obtained for different types of cancer shows that tumor initiation, progression, and therapeutic resistance are regulated by heat shock factor 1. This research aimed to analyze the effects of heat shock factor 1 on the biological behavior of oral squamous cell carcinoma. METHODS: Clinicopathological and immunoexpression study of heat shock factor 1 in 70 cases of oral tongue SCC and functional assays by gene silencing of this factor in an oral tongue SCC cell line. RESULTS: Heat shock factor 1 was overexpressed in oral tongue SCC specimens compared to normal oral mucosa (p < 0.0001) and in the SCC15 line compared to immortalized keratinocytes (p < 0.005). No significant associations were observed between overexpression of heat shock factor 1 and clinicopathological parameters or survival rates of the oral tongue SCC cases in the present sample. In vitro experiments showed that heat shock factor 1 silencing inhibited cell proliferation (p < 0.005) and cell cycle progression, with the accumulation of cells in the G0/G1 phase (p < 0.01). In addition, heat shock factor 1 silencing reduced cell invasion capacity (p < 0.05) and epithelial-mesenchymal transition, characterized by a decrease in vimentin expression (p < 0.05) and an increase in E-cadherin expression (p < 0.001). CONCLUSION: Heat shock factor 1 may exert several functions that help maintain cell stability under the stressful conditions of the tumor microenvironment. Thus, strategies targeting the regulation of this protein may in the future be a useful therapeutic tool to control the progression of oral squamous cell carcinoma.

A Systematic Review of Adenoid Ameloblastoma: A Newly Recognized Entity.

BACKGROUND: Recently, a new odontogenic tumor has been described, the so-called adenoid ameloblastoma (AdAM). The aim of this review was to determine the clinical and imaging features of AdAM and to describe its main histopathological findings. METHODS: The systematic review included published cases with a diagnosis of AdAM in the gnathic bones, which had sufficient clinical, imaging, and histopathological data to confirm its diagnosis. The following histopathological diagnostic criteria were adopted: presence of ameloblastoma-like components, duct-like structures, spiral cellular condensations, and a cribriform architecture. RESULTS: Fifteen articles, corresponding to 30 cases of AdAM, were selected. Most cases affected men (63.3%), with a slight preference for the mandible (16:14) and the posterior region of gnathic bones was the most commonly affected site. The mean age at diagnosis was 40.8 years. Clinically, the lesions usually presented as a swelling (53.3%) and, radiographically, as a well-defined radiolucency (33.4%). Surgical resection (40%) was the most frequently adopted treatment and recurrence occurred in 30% of cases. Microscopic examination showed cribriform areas in most AdAM cases (93.3%); duct-like structures and spiral cellular condensations were seen in 100% of the cases. CONCLUSION: The small number of reported cases, the existence of erroneous diagnoses, and the adoption of initial conservative management make it difficult to determine whether AdAM has a higher risk of recurrence or more aggressive biological behavior than conventional ameloblastomas.

Peripheral dentinogenic ghost cell tumor-report of two cases and review of the literature.

Peripheral dentinogenic ghost cell tumor (DGCT) is a rare and non-aggressive benign odontogenic tumor. They usually affect the elderly and are predominantly located in the anterior region of the jaws. Their differential diagnosis includes reactive/inflammatory gingival lesions. We report here two cases of peripheral DGCT in a 73-year-old female and a 48-year-old male patient and review the cases published in the literature. Both lesions presented as a nodular lesion in the mandible, and panoramic radiography showed no abnormalities. Microscopically, it was observed to be an ameloblastomatous epithelial proliferation associated with clusters of ghost cells and dysplastic dentin. Immunohistochemistry revealed positivity for cytokeratin 19 and a low Ki-67 proliferative index. Based on histopathological features and the absence of radiographic findings, a diagnosis of peripheral DGCT was rendered. The low number of cases published of peripheral DGCT makes case reports important in providing information that helps in their diagnoses and management.

Histopathologic grading and its relationship with outcome in oral tongue squamous cell carcinoma.

BACKGROUND: Histopathologic grading has been routinely used as a complement for clinical staging in the prognostication of patients with oral tongue squamous cell carcinoma (OTSCC). However, this subject remains contentious because there is no universally accepted grading system. OBJECTIVES: This study compared the prognostic significance of four histopathologic grading systems in 80 cases of oral tongue squamous cell carcinoma (OTSCC). METHODS: Clinical and follow-up information of the patients were obtained from medical records. Histopathologic malignancy grading of the tumor invasive front, Histologic risk assessment (HRA), World Health Organization (WHO) grading system, and Budding and Depth of invasion (BD) model were evaluated in the surgical specimens. RESULTS: The HRA, histopathologic malignancy grading and WHO systems did not predict survival. Patients with larger tumor size [Hazard ratio (HR): 2.38; 95% confidence interval (CI): 1.07-5.27; P = 0.026] and patients with BD model high-grade tumors (HR: 2.99; 95% CI: 1.03-8.68; P = 0.034) were significantly associated with a poor 5-year overall survival rate. In the multivariate analysis, tumor size was identified as the only significant independent prognostic factor (HR: 2.23; 95% CI: 1.00-4.99; P = 0.050). None of the grading systems studied was associated with 5-year disease-free survival rates. CONCLUSIONS: BD model was the only histopathologic grading system associated with the outcome of patients with OTSCC, indicating its potential value as an effective tool for the prognostication of OTSCC.

Teratocarcinoma-derived growth factor-1 (Cripto-1) is overexpressed in epithelial odontogenic lesions displaying more aggressive behaviour.

PURPOSE: Cripto-1 also known as teratoma-derived growth factor 1 (TDGF-1) belongs to the EGF-CFC family of growth factor-like molecules. Cripto-1 is involved with embryonic development and not expressed in adult tissue, but some tumours are accompanied by reactivation. METHODS: The aim of this study was to evaluate the immunohistochemical expression of Cripto-1 in most common odontogenic cysts and tumours. Thirty ameloblastomas, 30 keratocysts, 30 dentigerous cysts and two ameloblastic carcinomas were evaluated using the polymeric immunoperoxidase technique. Immunohistochemical expressions were analysed by the IRS (immunoreactive score). Statistical analyses were performed by the Kruskal-Wallis and Mann-Whitney tests (p ≤ 0.05). RESULTS: Age ranged from 9 to 75 years old, with a prevalence of females (n = 49/53.3%). The mandible was the most affected anatomical site (n = 69/75.0%). Cripto-1 immunoexpression was observed in all ameloblastoma, keratocyst and ameloblastic carcinoma cases, although nine dentigerous cyst cases (30%) were negative. Expression scores were higher in ameloblastoma, keratocyst and ameloblastic carcinoma cases (median ranging from 8 to 11) when compared with dentigerous cyst cases (median of 2), with a statistically significant difference (p < 0.001). CONCLUSIONS: Cripto-1 is critically important in the progression of several tumours since it is related to significant cell survival and differentiation pathways. The high expression of Cripto-1 in more aggressive odontogenic lesions suggests that this molecule may be involved in the activation of important pathways related to the etiopathogenesis of these lesions.

Peripheral compound odontoma: A rare case report and literature review.

Peripheral odontoma is a very rare odontogenic hamartoma arising in soft tissues. Here, we report a case of peripheral odontoma in a pediatric patient and review the cases published in the literature. An 11-year-old male patient presented a nodular lesion in the anterior region of the palate for over 1 year. Under the clinical hypothesis of fibroma, an excisional biopsy was performed. Histopathological examination revealed the presence of tooth-like structures, formed by enamel, and dentin matrix, occasionally associated with the dental papilla and surrounding pulp tissue, thus, the histopathological diagnosis of peripheral odontoma was established. The patient has been undergoing follow-up for 6 months without any signs of lesion recurrence. Peripheral odontomas are uncommon lesions that usually affect young patients and display a preference for the maxilla and limited growth potential. The recognition of the clinical and histopathological features of the peripheral odontoma is indispensable for the establishment of its diagnosis.

Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland.

INTRODUCTION: Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. OBJECTIVE: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands. METHODS: A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0-3). For statistical analysis, Mann-Whitney and Kruskal-Wallis tests were performed and a significance level of p ≤ 0.05 was established. RESULTS: Most CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294). CONCLUSION: The results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.

Pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: E-cadherin immunoexpression and analysis of the CDH1 -160C/A polymorphism.

OBJECTIVE: Despite their similar cellular origin, pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC) present distinct behaviors. This study aimed to analyze the immunoexpression of E-cadherin in PA and ACC of salivary glands, and to investigate differences in its expression in relation to E-cadherin gene (CDH1) -160C/A polymorphism. DESIGN: Twenty-four PA (15 cell-rich and 9 cell-poor tumors) and 24 ACC (10 tubular, 8 cribriform and 6 solid tumors) were selected for the analysis of pattern of distribution, and cellular localization of E-cadherin. In addition, E-cadherin expression was evaluated using the H-score scoring system. The CDH1 -160C/A polymorphism was investigated by PCR-RFLP. RESULTS: No significant differences in pattern of distribution (p=0.181) and cellular localization (p=0.192) of E-cadherin were observed between PA and ACC. Comparison of PA and ACC cases revealed a higher median H-score in the latter (p=0.036). Cell-rich PA presented a higher H-score than cell-poor tumors (p=0.013), whereas no significant differences in E-cadherin expression were observed between ACC subtypes (p=0.254). The heterozygous genotype of the CDH1 -160C/A polymorphism was detected in only one PA and one ACC. H-scores for tumors carrying the polymorphism were below the lower quartile of their respective groups. CONCLUSIONS: The results suggest that E-cadherin expression in PA and ACC is mainly related to cellular composition (epithelial cells versus myoepithelial cells) and degree of differentiation of myoepithelial cells in these tumors. The CDH1 -160C/A polymorphism does not seem to significantly influence the expression of E-cadherin in PA and ACC of salivary glands.

Histopathological review of 667 cases of oral mucoceles with emphasis on uncommon histopathological variations.

Mucoceles can occur in the oral cavity, appendix, bladder, paranasal sinuses, and lacrimal sac. In the oral cavity, mucoceles arise from pathological alterations in the minor salivary gland ducts. In this study, we aimed to histologically reevaluate cases of oral mucoceles to identify possible variants. A total of 667 slides containing tissue sections stained with hematoxylin and eosin diagnosed as a phenomenon of mucus extravasation were analyzed under light microscopy by 4 previously trained examiners. In 128 cases (19.1%), 1 or more histopathological changes were identified. Twenty cases (2.9%) exhibited collagenous globular structures compatible with myxoglobulosis. In 30 cases (4.49%), dissociation of collagen fibers after mucin extravasation was observed. Fifty-four cases (8.09%) exhibited papillary synovial metaplasia-like change, and 32 (4.79%) showed a significant reduction in the lumen of the cavity due to large papillae. Twenty cases (2.9%) were compatible with superficial mucoceles, and in 11 cases (1.64%), the foamy macrophages showed an unusual solid arrangement, known as clear cell change. It is essential to recognize the possible histopathological changes in oral mucoceles to avoid diagnostic pitfalls.

Epidemiological survey of mucus extravasation phenomenon at an oral pathology referral center during a 43 year period.

INTRODUCTION: Mucoceles are common benign pseudocystic lesions of the oral cavity; their main etiological factors are trauma and ductal obstruction. Two histological patterns are found: mucus retention phenomenon (MRP) and mucus extravasation phenomenon (MEP). Mucus extravasation phenomenon is the more common histological subtype and it mainly affects the lower lip. The knowledge of its main clinical features and management is important to assist health professionals in clinical practice. OBJECTIVE: This study aimed to determine the relative frequency and distribution of oral mucoceles in an oral pathology reference center. METHODS: Cross-sectional historical study that analyzed all cases pathologically diagnosed as mucus extravasation phenomenon by the department of anatomic pathology of an oral pathology referral center from June of 1970 to May of 2014, considering the clinical characteristics of the lesion and those relating to the patient. SPSS v. 20.0 software for Windows was used for descriptive analysis. RESULTS: During 43 years, 719 cases of mucus extravasation phenomenon (54.7% men and 45.3% women) were registered, with the lower lip as the most commonly affected site (n=484; 67.3%). The average age of patients was 20.8 years (SD±14.4) with a peak occurrence in the second decade of life. Most professionals had oral mucocele/ranula (n=606; 84.3%) as the initial clinical impression. CONCLUSION: Mucus extravasation phenomenon is a lesion that primarily affects young patients, affecting mainly the lower lip, and is commonly found in oral diagnostic services.

Association of the XPD and XRCC3 gene polymorphisms with oral squamous cell carcinoma in a Northeastern Brazilian population: A pilot study.

OBJECTIVE: to evaluate the association between XPD and XRCC3 polymorphisms and oral squamous cell carcinoma (OSCC). DESIGN: the sample consisted of 54 cases of OSCC and 40 cases of inflammatory fibrous hyperplasia (IFH). Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: XPD-Lys/Gln was more common in IFH (n=28; 70%) than in OSCC (n=24; 44.4%) (OR: 0.3; p<0.05). XPD-Gln was more frequent in high-grade lesions (0.48) than in low-grade lesions (0.21) (OR: 3.4; p<0.05). The Gln/Gln genotype was associated with III and IV clinical stages (OR: 0.07; p<0.05). XRCC3-Met was more frequent in OSCC (0.49) than in IFH (0.35) (OR: 2.6; p<0.05). The Met/Met genotype was associated with the presence of metastases (OR: 8.1; p<0.05) and with III and IV clinical stages (OR: 0.07; p<0.05). CONCLUSIONS: in this sample, the frequency of XPD-Gln in IFH suggests that this variant may protect against OSCC. The presence of the XRCC3-Met allele seems to contribute to the development of OSCC, metastases and more advanced stages in these lesions.

Hyaline ring granuloma of vegetable: Report of two cases with histochemical and immunohistochemical study.

BACKGROUND: Peripheral hyaline ring granuloma is a rare lesion characterized by the presence of hyaline rings and multinucleated giant cells. Its pathogenesis is related to exogenous factors such as vegetal origin, resulting in foreign body reaction mediated by macrophages against cellulose particles. We report two cases: a 58-year-old male with a lesion in the maxillary alveolar mucosa measuring 1.0cm×1.0cm; and a 50-year-old female presenting a slight swelling in the alveolar mucosa, measuring 0.7cm×0.7cm and diagnosed as asymptomatic sessile nodule of fibrous consistency. Microscopic examination revealed a dense connective tissue with focal area of concentric hyaline collagen deposition and multinucleated giant cell granulomas of foreign body type. Immunohistochemical study was positive for anti-CD68/anti-α-SMA, confirming the foreign body reaction and vascular integrity. Histochemical analysis for PAS with and without diastase and van Gieson highlighted the vegetable exogenous origin of foreign material. Additionally, we performed a review of 7 cases published in the literature in the last 10 years.

Participation of hMLH1, p63, and MDM2 proteins in the pathogenesis of syndromic and nonsyndromic keratocystic odontogenic tumors.

OBJECTIVES: To evaluate the expression of hMLH1, p63, and MDM2 in Gorlin syndrome-associated keratocystic odontogenic tumors (SKOTs) and nonsyndromic keratocystic odontogenic tumors (NSKOTs). STUDY DESIGN: Seventeen primary NSKOTs, 17 SKOTs, and 8 recurrent NSKOTs were analyzed by using immunohistochemistry. RESULTS: No significant differences in the hMLH1, p63, or MDM2 labeling indices were observed between groups (P = .398; P = .232; P = .426, respectively). Higher hMLH1 immunoexpression was found in the basal layer of primary NSKOTs. Most KOTs exhibited p63 immunoexpression in the upper layers of the epithelium. MDM2 immunoexpression was observed in the upper epithelial layers of SKOTs and recurrent NSKOTs. CONCLUSION: It was not possible to correlate the immunoexpression of hMLH1, p63, and MDM2 in SKOTs and primary and recurrent NSKOTs, suggesting that these proteins exert independent effects on the development of these groups of tumors.

Stromal myofibroblasts in potentially malignant and malignant lesions of the oral cavity.

Previous studies have demonstrated that myofibroblasts in the adjacent stroma are involved in the development and progression of malignant tumors. The aim of this study was to investigate the involvement of myofibroblasts in the progression of oral squamous cell carcinomas (OSCCs) by determining myofibroblast density in potentially malignant and malignant oral lesions. A total of 69 potentially malignant oral lesions (leukoplakias with mild, moderate or severe dysplasia), 90 OSCCs (well-, moderately and poorly differentiated), eight oral verrucous carcinomas and 29 fibrous hyperplasias were examined for the presence of myofibroblasts using immunohistochemical detection of isoform α of smooth muscle actin. Myofibroblasts were not identified in the adjacent stroma of fibrous hyperplasias and potentially malignant oral lesions, whereas 59.8% of the oral carcinomas exhibited myofibroblasts in various densities. The density was significantly higher in moderately and poorly differentiated OSCCs when compared with well-differentiated tumors (P=0.04 and P=0.007, respectively). In verrucous carcinomas, the specific variant of well-differentiated OSCC, stromal myofibroblasts were not detected. The results of the present study demonstrated that immunodetection of myofibroblasts does not aid with the determination of the malignant transformation potential of oral dysplasias, although moderately and poorly differentiated tumors exhibited a significantly higher density of myofibroblasts. The results reinforce the hypothesis that myofibroblasts may contribute to oral tumorigenesis, indicating that verification and monitoring of such may serve as a putative marker of OSCC behavior.

Actinic cheilitis: clinicopathologic profile and association with degree of dysplasia.

BACKGROUND: Actinic cheilitis (AC) is a potentially malignant disorder of the lip caused by exposure to solar radiation. OBJECTIVES: This study was conducted to evaluate the clinicopathologic profile of cases of AC and to verify associations with the degree of dysplasia. METHODS: This retrospective study analyzed data for 40 patients with AC. Demographic, clinical, and histopathologic data were evaluated. Sections measuring 5 µm in thickness were cut, deparaffinized, and stained with hematoxylin and eosin for histologic examination. The degree of epithelial dysplasia was graded using the criteria defined by the World Health Organization. Two calibrated oral pathologists analyzed the slides. RESULTS: Analysis of the AC patients sampled showed that 75.0% were male (P=0.002), 80.0% were aged≥40 years (P<0.001), 74.3% were Caucasian (P=0.004), and 68.6% had occupational exposure to sunlight (P=0.028). The most common clinical manifestation was white lesions (55.0%), and 40.0% of patients had no dysplasia. No significant associations emerged between the histologic grading of AC and gender (P=1.000), age (P=1.000), ethnicity (P=0.416), occupational exposure to sunlight (P=1.000), and clinical presentation (P=0.467). CONCLUSIONS: The degree of dysplasia in AC was not statistically associated with gender, age, ethnicity, occupational exposure to sunlight, or clinical appearance. This study provides some support for the hypothesis that clinicopathologic features are not related to the degree of dysplasia in AC.

Relationship between the epithelial expression of hMLH1, MDM2, and p63 and lower lip carcinogenesis.

OBJECTIVES: To evaluate the relationship between the epithelial expression of hMLH1, MDM2, and p63 in lower lip carcinogenesis, comparing the immunostaining of these proteins in cases of actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC). STUDY DESIGN: Forty cases of AC and 40 cases of SCC were studied, both lesions were of lower lip. Histological sections of 3 µm were submitted to immunoperoxidase method, and 1000 cells were counted for immunohistochemical analysis of lesions. The results were analyzed quantitatively, and expression was compared by the Mann-Whitney, Student t-test, or one-way ANOVA, adopting a level of significance of 5%. RESULTS: A higher percentage of epithelial cells expressing hMLH1 was observed in cases of AC without dysplasia or mild dysplasia (721.23 ± 88.116), whereas fewer positive cells were observed in lower lip SSCs (255.03 ± 199.47) when compared to the AC group (P < 0.001). Immunoexpression of MDM2 was higher in SCCs of the lower lip compared with AC (P = 0.019). For p63 protein, the expression was higher in AC than in SCC (P = 0.045). CONCLUSION: The present results showed changes in the immunoexpression of hMLH1, MDM2, and p63 in epithelial cells from premalignant and malignant lip disease, supporting the hypothesis that these alterations are related to the process of lower lip carcinogenesis.

Analysis of CD8+ and CD4+ cells in oral squamous cell carcinoma and their association with lymph node metastasis and histologic grade of malignancy.

This study aimed to analyze CD8 and CD4 cells in oral squamous cell carcinoma and to correlate it with prognostic indicators. The sample was composed of 50 cases. Clinical data and histologic grade of malignancy were obtained. Specimens were submitted to immunohistochemistry. Cells were counted in 10 fields at the tumor invasion front and expressed as median. CD8 cells were more frequent in nonmetastatic lesions (18.5) and in low-grade specimens (18.2) (P<0.05). CD4 cells were equally distributed in nonmetastatic and metastatic lesions (4.5). In addition, they were slightly more frequent in low-grade lesions (4.7). None of these correlations were significant (P>0.05). CD8/CD4 ratio was higher in cases without metastasis (3.57) and in low-grade lesions (3.62) (P>0.05). Probably, CD8 cells are the most effective and important cells in the host immune responses against oral squamous cell carcinoma. In addition, CD4 cells could indirectly influence the host protection through regulation of CD8 recruitment and activation.

Maxillary cementoblastoma in a child.

Cementoblastoma is a rare benign tumor that almost always occurs in the premolar or molar region and more commonly in the mandible than in the maxilla. We present a unique incisor maxillary cementoblastoma in an 11-year-old child not previously described. To our knowledge, only 2 maxillary cases, both related to canine teeth, were described in the international literature. Thus, the aim of this article was to discuss the clinical presentation, diagnosis, and subsequent treatment of a patient with a cementoblastoma in the anterior maxillary region.

Sialolipoma of minor salivary glands.

Sialolipoma is a recently described histologic variant of lipoma and is characterized by well-demarcated proliferation of mature adipocytes with secondary entrapment of salivary gland elements. These tumors have been observed in both the major and minor salivary glands, with more than 20 cases being reported in the English literature. In general, the clinical presentation of sialolipomas of the minor salivary glands suggests a diagnostic hypothesis of salivary gland lesions, commonly neoplasms. In the major salivary glands, the clinical features suggest either a salivary gland neoplasm or a lipoma. Surgical excision is the treatment of choice for sialolipomas, with no reports of recurrence or malignant transformation. The present article reports 4 additional cases of sialolipoma, all of them affecting the minor salivary glands, and reviews the literature regarding clinicopathologic aspects, differential diagnosis, and therapeutic management of this recently recognized histologic variant of lipoma.

Bone morphogenetic protein-2/4 and bone morphogenetic protein receptor type IA expression in metastatic and nonmetastatic oral squamous cell carcinoma.

PURPOSE: The study aimed to analyze the expression of bone morphogenetic protein-2/4 (BMP-2/4) and its receptor BMPR-IA (BMP receptor type IA) in metastatic and nonmetastatic oral squamous cell carcinoma (OSCC) and its implications for disease prognosis. MATERIALS AND METHODS: The experimental group included 16 cases of OSCC without metastasis and 7 cases of OSCC with metastasis. The presence or absence of nodal metastasis was used as a parameter for the evaluation of disease prognosis. Ten cases of oral fibroepithelial hyperplasia were selected as the control group. The expression of BMP-2/4 and BMPR-IA was analyzed by immunohistochemistry. RESULTS: In the experimental group with metastasis, strong expression of BMP-2/4 was observed in most cases (71.4%), whereas BMPR-IA exhibited weak expression (85.7%). In the experimental group without metastasis, there was strong expression of BMP-2/4 (62.5%) and BMPR-IA (100%). A significant association was observed between the prognosis of OSCC and the intensity of BMP-2/4 staining (P = .002). Weak immunoreactivity to BMP-2/4 and BMPR-IA was observed in all control specimens. CONCLUSIONS: The results suggest that strong expression of BMP-2/4, associated with low expression of BMPR-IA, observed in metastatic OSCC has a prognostic value, with the loss of responsiveness to BMPs through the loss of expression of their receptors being indicative of the development of metastasis.