Ru-Cheng Kuo

Prognostic role of p27Kip1 expression in oral squamous cell carcinoma in Taiwan

The cyclin-dependent kinase inhibitor p27(Kip1) can inhibit the G1 to S transition of the cell cycle and is a putative tumor suppressor. Decreased expression of p27(Kip1) protein has been correlated with poor prognosis in a variety of human tumors. We examined the expression of p27(Kip1) in oral squamous cell carcinoma (SCC), epithelial dysplasia (ED) and normal oral mucosa (NOM) using antibodies to p27(Kip1). Positive p27(Kip1) nuclear staining was detected in all the specimems from ED and NOM, whereas positive p27(Kip1) staining was observed in 16 of the 63 (25%) cases of oral SCC. The labeling index for p27(Kip1) protein was significantly reduced from NOM through ED to oral SCCs, indicating that changes of p27(Kip1) protein expression may be an early event in oral carcinogenesis in Taiwan. The Kaplan-Meier analysis showed patients with p27(Kip1)-positive tumors had significantly higher overall survival than those with p27(Kip1)-negative tumors in a total of 63 patients (P=0.015) and 47 patients with areca quid chewing habit (P=0.026). Multivariate analysis showed decreased p27(Kip1) protein expression was an independent significant predictor of poor overall survival in the patients with oral SCCs. These results indicate that p27(Kip1) protein expression may serve as a putative new adjuvant prognostic marker for routine assessment of oral SCC patients.

Oral verrucous hyperplasia: histologic classification, prognosis, and clinical implications

BACKGROUND Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. METHODS Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed. RESULTS We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 +/- 7 months. The mean time for malignant transformation was 22 +/- 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy. CONCLUSIONS We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.

Prompt healing of erosive oral lichen planus lesion after combined corticosteroid treatment with locally injected triamcinolone acetonide plus oral prednisolone.

BACKGROUND/PURPOSE Erosive oral lichen planus (EOLP) is a T-cell-mediated inflammatory disease that is refractory to treat. This study tested whether local injection of triamcinolone acetonide plus oral administration of low- or medium-dose prednisolone could hasten the healing of EOLP lesions. METHODS In this study, 50 EOLP patients were treated with local injection of Kenacort A (40 mg triamcinolone acetonide once weekly for 3 and 2 weeks for 30 major and 20 minor EOLP patients, respectively) plus oral administration of prednisolone (25-30 mg and 15-20mg of prednisolone once daily for 2 weeks for 30 major and 20 minor EOLP patients, respectively). The oral administration of prednisolone was tapered to 5mg per day and stopped in 7 days. Then, the patients were treated with topical Dexaltin (0.1% dexamethasone, once or twice per daily) and oral administration of vitamin Bc (one capsule twice daily) thereafter. RESULTS After 3-week treatments, the 30 major EOLP patients showed complete response (lack of detectable erosive or ulcerative lesion with absence or regression of reticular or papular OLP) in 27 cases (90%) and partial response (reduction of erosive or ulcerative lesion by at least 30% in diameter with regression of reticular or papular OLP) in cases (10%); and 20 minor EOLP patients demonstrated complete response in 18 cases (90%) and partial response in two cases (10%). However, all the 45 complete response major or minor EOLP patients showed recurrence of erosive or ulcerative lesion after 3-24 (mean 12) months of follow-up. CONCLUSION Prompt and complete healing of the EOLP lesions could be achieved in a relative short period of time after treatment with our protocol. Although complete response EOLP lesions recurred after a follow-up period of 3-24 months, patients did have an average remission period of 12 months after treatment with our protocol.

Odontogenic Fibroma: A Clinicopathological Study of 15 Cases

BACKGROUND/PURPOSE Odontogenic fibroma (ODF) is a rare odontogenic tumor. It can be further divided into peripheral odontogenic fibroma (PODF) and central odontogenic fibroma (CODF). This retrospective study evaluated the clinical and histopathological features of 15 ODFs in Taiwanese patients. METHODS Fifteen consecutive cases of ODF were collected from 1984 to 2009. The clinical data and microscopic features of these cases were reviewed and analyzed. RESULTS Twelve PODFs were excised from six male and six female patients (mean age: 35 years) and three CODFs from two male and one female patients (mean age: 11 years). Eight of the 12 PODFs were found on the mandibular gingiva and four on the maxillary gingiva, with the most common site being the mandibular anterior and premolar region (5 cases). Two CODFs were located in the molar region of the mandible and one in the anterior maxilla. Two CODFs showed a mixed lesion and one a radiolucent lesion. No recurrence of the 15 ODFs was found after total excision or enucleation. Microscopically 58.3% of the PODFs showed surface ulcèration. Calcified foci composed of osteoid, cementoid, or cementicle-like materials were noted in all 15 ODFs. Nests or strands of odontogenic epithelium were found in all 15 ODFs. The stromal component was mainly fibro-collagenous in nine of the 12 PODFs, whereas two of the three CODFs contained predominantly myxomatous stroma. CONCLUSION PODFs occurred more commonly than CODFs. PODF showed an equal sex distribution and was found more frequently in patients in the third to fourth decades of life. The most commonly affected site was the mandibular gingiva, especially the anterior and premolar gingiva. Only three CODFs were found; therefore, we could not draw any conclusions about CODF in Taiwanese patients.

Clinicopathological Study of Oral Giant Cell Fibromas

BACKGROUND/PURPOSE Oral giant cell fibromas (GCFs) are found predominantly in Caucasians and rarely in other races. This retrospective study evaluated the clinicopathological features of 24 GCFs in Taiwanese patients. METHODS Twenty-four consecutive cases of oral GCF were investigated from 1987 to 2008. Clinical data and microscopic features were reviewed and analyzed. RESULTS The mean age of patients at the time of diagnosis was 29 years. Oral GCF occurred more commonly in patients between 11 and 40 years of age. There were 12 male and 12 female patients. The lesions were found more frequently on the tongue (8 cases) and gingiva (7 cases). The mean size of the lesion was 5.5mm (range, 2-10 mm) in greatest dimension. GCF is misdiagnosed frequently as fibroma (19 cases) or papilloma (5 cases). All tumors were treated by total surgical excision and no recurrence was found after treatment. Microscopically, the GCF was a sessile or pedunculated mass covered with a thin layer of parakeratinized or orthokeratinized stratified squamous epithelium. The tumor was composed mainly of loose or dense fibrous connective tissue with well-formed capillaries and no inflammation. The consistent and diagnostic feature was the presence of large stellate giant cells, usually with one or two nuclei. Multinucleated giant cells were seen occasionally. These giant cells were most numerous in the connective tissue just beneath the epithelium. CONCLUSION Oral GCFs show no significant sex predilection and occur in patients in the second to fourth decades of life. Usually, the lesions are < 1 cm in diameter and are found more frequently on the tongue and gingiva. GCF resembles fibroma or papilloma and is difficult to diagnose correctly at the first glance. All GCFs can be treated by conservative surgical excision without subsequent recurrence.

Clinicopathological Study of 252 Jaw Bone Periapical Lesions From a Private Pathology Laboratory

BACKGROUND/PURPOSE Periapical lesions are common sequelae of pulp diseases. This retrospective study evaluated the clinical and histopathological features of periapical lesions sent to a private pathology laboratory by dentists in private clinics. METHODS Two hundred and fifty-two consecutive cases of periapical lesions were collected from September 2005 to October 2009. Clinical data and histopathological features of these periapical lesions were reviewed and analyzed. RESULTS The 252 periapical lesions consisted of 128 periapical granulomas, 117 periapical cysts, and seven periapical scars. These 252 lesions were taken from 252 patients (92 men and 160 women; mean age = 43.6 years; range, 9-81 years). Of the 252 periapical lesions, 186 were found in the maxilla and 66 in the mandible. The most common site for periapical lesions was the maxillary anterior region (134 cases, including 73 granulomas, 54 cysts and 7 scars), and the most frequently involved tooth was the maxillary lateral incisor (64 cases, including 29 granulomas, 31 cysts and 4 scars). Of the 117 periapical cysts, 116 were lined by stratified squamous epithelium and one by mucoepidermoid epithelium. Hyaline bodies were discovered in the lining epithelium of four periapical cysts. Odontogenic epithelial rest, cholesterol cleft, foamy histiocytes, hemosiderin-laden macrophages, dystrophic calcification, foreign bodies, and bacterial clumps were found in five, three, nine, two, 28, 10 and one periapical granulomas, respectively, as well as in six, 11, eight, seven, 19, nine and eight periapical cysts, respectively. CONCLUSION Granulomas and cysts were the two most common periapical lesions. Periapical lesions occurred more frequently in female patients and in those in their fourth to fifth decades. The most commonly affected site for periapical lesions was the maxillary anterior region, and the most frequently involved tooth was the maxillary lateral incisor.

Successful treatment of an early invasive oral squamous cell carcinoma with topical 5-aminolevulinic acid-mediated photodynamic therapy

Our previous studies showed successful treatment of a series of 36 oral verrucous hyperplasia lesions and of an extensive oral verrucous carcinoma with a topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (topical ALA-PDT) protocol (with a fluence rate of 100 mW/cm 2 and a light exposure dose of 100 J/cm 2 ) using a 635-nm light-emitting diode (LED) light source. In this case report, we tested whether an enhanced topical ALA-PDT protocol (with a fluence rate of 200 mW/cm 2 and a light exposure dose of 200 J/cm 2 ) could be used to treat an early invasive oral squamous cell carcinoma (OSCC) with a verrucous appearance of the left lower posterior edentulous alveolar mucosa of a 67-year-old male former areca-quid chewer and ex-smoker. The main verrucous lesion showed complete regression after eight treatments with PDT. However, 10 extra treatments were needed to eradicate the multiple residual leukoplakia lesions on the edentulous alveolar mucosa. Moderate to severe post-PDT pain was noted during the initial eight treatments, and the patient needed analgesics (codeine phosphate, 30 mg three times daily) to control the pain. No recurrence of the OSCC lesion was found after a follow-up period of 4 years. We suggest that our enhanced topical ALA-PDT protocol may have good potential to be used as a treatment of choice for a superficially invasive OSCC without regional or distant metastasis before the commencement of other effective therapies.

Nuclear Expression of metastasis-associated Protein 1 (MTA1) is Inversely Related to Progression of Oral Squamous Cell Carcinoma in Taiwan

Overexpression of metastasis-associated protein 1 (MTA1) has been demonstrated in a variety of human cancers and found to be significantly associated with the tumor size, lymph node metastasis, clinical stage, tumor invasion, and prognosis of these cancers. In this study, we examined the expression of MTA1 in 74 specimens of oral squamous cell carcinoma (OSCC), 100 specimens of oral epithelial dysplasia (OED; 33 mild, 44 moderate, and 23 severe OED cases), and 21 specimens of normal oral mucosa (NOM) by immunohistochemistry. The cytoplasmic and nuclear MTA1 labeling indices (LIs) in OSCC, OED, and NOM samples were calculated and compared among these groups. Correlations of the cytoplasmic and nuclear MTA1 LIs in OSCC with clinicopathological parameters and survival of OSCC patients were statistically analyzed. We found that the mean cytoplasmic MTA1 LIs were all over 95% for the NOM, OED, and OSCC samples. There were no significant associations of the cytoplasmic MTA1 LI with any of the clinicopathological parameters of OSCC patients. The mean nuclear MTA1 LIs significantly decreased from NOM (73%±13%) to mild OED (71%±16%), moderate OED (60%±22%), and severe OED (46%±25%) and OSCC samples (30%±30%, p＜0.001). A significant correlation was found between the lower mean nuclear MTA1 LIs and OSCCs located on the buccal mucosa and tongue (p=0.001), with larger tumor sizes (T3 and T4, p=0.020), with regional lymph node metastases (N1, N2, and N3, p=0.024), and with more-advanced clinical stages (stages 3 and 4, p=0.045). Our results suggest that MTA1 is universally expressed in the cytoplasm of normal, dysplastic, and malignant oral epithelial cells. The nuclear expression of MTA1 significantly dropped from NOM through OED to OSCC samples, and was inversely related to the T status, N status, and clinical staging of OSCCs. Therefore, the nuclear MTA1 LI can be used to predict the progression of OSCCs in Taiwan.

Expression of p34(superscript cdc2) in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Overexpression of p34(superscript cdc2) has been demonstrated in a variety of human cancers and found to be significantly associated with the tumor size, lymph node metastasis, clinical stage, and prognosis of these cancers. In this study, we examined the expression of p34(superscript cdc2) in 81 specimens of oral squamous cell carcinoma (OSCC), 9S specimens of oral epithelial dysplasia (OED; 29 mild, 43 moderate, and 23 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemisry. The cytoplasmic p34(superscript cdc2) labeling indices (LIs) in OSCC, OED, and NOM samples were calculated and compared among the groups. Correlations of the cytoplasmic p34(superscript cdc2) LIs in OSCCs with clinicopathological parameters and survival of OSCC patients were analyzed statistically. We found that the mean cytoplasmic p34(superscript cdc2) LIs significantly increased from NOM (6±7%) through mild (18%±10%), moderate(23%±11%), and severe OED (40%±22%) to OSCC samples (73%±20%, p=0.000). A significant correlation was found between the higher mean cytoplasmic p34(superscript cdc2) LIs and positive regional lymph node metastases (p=0.013), more-advanced clinical suggest (P=0.022), and higher differentiation of cancer cells (p =0.027). Our results suggest that the p34(superscript cdc2) expression is an early event in oral carcinogenesis and may play an important role in oral carcinogensis. Cytoplasmic p34(superscript cdc2) LIs can be used as a biomarker to predict the progression of OSCCs in Taiwan.

Oral Neurilemmomas-A Clinicopathological Study of 21 Cases

Oral neurilemmomas (ON) are rare oral lesions. Twenty-one cases of ONs diagnosed and treated in our institute during the period from January 1991 to June 2004 were analyzed in this study. There were 14 male and 7 female patients. The mean age of the 21 patients at the time of diagnosis was 30 (range, 14-67) years with a peak incidence of tumor occurrence in the third decade. The more-common sites for an ON were the tongue (8 cases) and buccal mucosa (5 cases). The clinical appearance of ONs was frequently a pink, movable mass. In only 1 case was palpation tenderness noted. The greatest dimension of the lesion was 2 cm with a mean of 1.0±0.5 cm. The duration of the lesion ranged from 10 days to 10 years with a median of 6 months. Of the 21 cases, the clinical diagnosis was a fibroma in 6, a mucocele in 4, a tongue or buccal tumor in 5, and others in 6. Surgical excision was the treatment of choice for all 21 lesions. None of the lesions showed recurrence after surgical excision. On the average, our 21 ONs contained 77%±16% Antoni A tissue and 23%±16% Antoni B tissue. We conclude that ONs occur most often in the third decade. The more-commonly affected sites are the tongue and buccal mucosa. ONs often present as a painless and movable mass which is very difficult to diagnose just based on their clinical features. Our ONs were mostly composed of Antoni A tissue, with much-smaller content of Antoni B tissue.