Biopsy Specimens Of Oral Mucosa Research Articles

Immunohistochemical study of Ki-67, PHH3, and CK15 protein expression in oral epithelial malignancy

To investigate the expression of Ki-67, phosphohistone H-3 (PHH3), and cytokeratin 15 (CK15) proteins in the cells of the oral mucosa (OM) according to the degree of its malignant transformation. OM biopsy specimens from 69 patients diagnosed with focal epithelial hyperplasia, intraepithelial squamous cell neoplasia, cancer in situ, and squamous cell carcinoma were examined. Tissue antigens were determined using mouse Ki-67 monoclonal antibodies, rabbit PHH3 polyclonal antibodies, and mouse CK15 monoclonal antibodies. There was an increase in epithelial proliferative and mitotic activities in squamous cell carcinoma and a sharp decrease in the expression of CK15 in the cytoplasm in cancer in situ and squamous cell carcinoma of the OM. The protein CK15 can be used for the differential diagnosis between high-grade dysplasia and OM epithelial malignancy at the stage of carcinoma in situ and squamous cell carcinoma.

Evaluation of protein kinase CK2 as a therapeutic target for squamous cell carcinoma of cats.

OBJECTIVE To investigate protein kinase CK2 (CK2) expression in squamous cell carcinoma (SCC) of cats and to examine effects of CK2 downregulation on in vitro apoptosis and viability in SCC. SAMPLE Biopsy specimens of oral mucosa and testis and blood samples from clinically normal cats, biopsy specimens of oral SCC from cats, and feline SCC (SCCF1) and mammary gland carcinoma (K12) cell lines. PROCEDURES Immunohistochemical labeling for CK2α was performed on biopsy specimens. Sequences of the CK2α subunit gene and CK2α' subunit gene in feline blood and feline cancer cell lines were determined by use of PCR and reverse-transcription PCR assays followed by direct Sanger sequencing. Specific small interfering RNAs (siRNAs) were developed for feline CK2α and CK2α'. The SCCF1 cells were treated with siRNA and assessed 72 hours later for CK2α and CK2α' expression and markers of apoptosis (via western blot analysis) and for viability (via 3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium assays). RESULTS CK2α was expressed in all feline oral mucosa samples and 7 of 8 oral SCC samples. Expression of CK2α and CK2α' was successfully downregulated in SCCF1 cells by use of siRNAs, which resulted in decreased viability and induction of apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE In this study, CK2 appeared to be a promising therapeutic target for SCCs of cats. A possible treatment strategy for SCCs of cats would be RNA interference that targets CK2.

The histological characteristics of clinically normal mucosa adjacent to oral cancer

The 'field cancerization' theory tries to explain the risk of local recurrences and development of second primary tumors in oral sqamous cell carcinoma (OSCC) patients. According to this theory it is assumed that clinically normal mucosa adjacent to oral cancer, except molecular, has already developed certain premalignant histopathological changes. The aim of this study was to determine histological characteristics of clinically normal-looking mucosa at different distances from the apparent tumor lesion margins in OSCC patients. Normal-appearing oral mucosa biopsy specimens were obtained from 30 new (untreated) oral cancer patients from sites at a distance of 10 mm and 20 mm from the tumor lesion margins and were compared with normal oral mucosa from 30 control patients with benign oral lesions. A total of 21 patients (70%) in the OSCC group demonstrated histological abnormalities under microscopic examination versus 7 (23.3%) control patients (P<0.01). Seventeen oral cancer patients (57%) showed significant difference in incidence and type of histological changes of normal-looking mucosa at a distance of 10 mm from the tumor lesion; 8 (27%) demonstrated reactive changes, 6 (20%) mild dysplasia and 3 (10%) squamous cell carcinoma, compared to histological abnormalities registered in 11 (OSCC) patients (36%) at a distance of 20 mm from the tumor; 10 (33%) displayed reactive changes and 1 (3%) mild dysplasia. Histological abnormalities of clinically normal-looking oral mucosa taken at different distances from the tumor lesion indicated the existence of subclinical field change and represent an important parameter during the assessment of the adequacy of surgical resection margins in oral cancer management.

Expression of stromal CD34 and α-smooth muscle actin in oral invasive cancer

To observe the expression of stromal CD34 and alpha-smooth muscle actin (alpha-SMA) in oral invasive cancer. The distribution and expression of stromal CD34 and alpha-SMA in 60 patients with invasive oral squamous cell cancer and 20 resections with tumor-free margins from 60 patients with invasive oral squamous cell cancer were examined by immunohistochemistry SP method. Twenty cases of resections of mucosa with tumor-free margins exhibited CD34 expression in fibrocytes cytoplasm in the vicinity of vessels, mucosa and submucosa but were free of alpha-SMA expression, only the walls of muscularized vessels stained positive for alpha-SMA in the stroma. Sixty invasive oral squamous cell carcinomas were free of stromal CD34 expression, only the endothelia of small vessels stained positive for CD34, of which 53 invasive oral squamous cell carcinomas expressed stromal alpha-SMA in myofibroblasts cytoplasm. The detection of CD34 and alpha-SMA is an adjunctive tool in judging oral cancer invasion in small oral mucosa biopsy specimens based on the absence of CD34 expression paralleled by the gain of alpha-SMA in the stroma of oral invasive cancer.

Apoptosis in oral erythema multiforme

Objective. Cell death was evaluated in oral erythema multiforme to test the hypothesis that apoptosis may be a mechanism by which keratinocytes die in this condition. Study design. Ten erythema multiforme and five control oral mucosa biopsy specimens were evaluated in immunohistochemically stained sections for apoptosis-regulating proteins Bcl-2, Bcl-x, Bax, p53, Fas, and Fas-ligand. Apoptotic keratinocytes, determined by a detection method for DNA fragmentation (TUNEL) and by conventional morphologic criteria were counted per high power field. Results. Keratinocyte staining for Bcl-2 protein was comparable in erythema multiforme and controls. Bcl-x expression was reduced in five erythema multiforme cases. Staining for Bax protein differed in six erythema multiforme cases and showed variable intensity in layers under the parakeratin. Only slight differences in staining patterns of Fas and Fas-ligand proteins were noted between erythema multiforme and controls. The number of apoptotic keratinocytes evaluated by morphologic examination was significantly higher in erythema multiforme (mean per high power field, 0.90 ± 0.2; controls, 0.06 ± 0.04; p < 0.05, Mann-Whitney test) and was limited in significance by the TUNEL method (erythema multiforme, 0.43 ± 0.1; controls, 0.02 ± 0.02). Overexpression of p53 protein was seen in basal keratinocytes in five erythema multiforme specimens (mean, 17.5 ± 4.03 per high power field; controls 1.2 ± 0.3). Conclusions. There is evidence that cell death in erythema multiforme is at least in part due to apoptosis. The apoptotic mechanism may be related to an altered expression of apoptosis-regulating proteins. Although measurable alterations in the phenotypic expression of Fas and Fas-ligand proteins were not apparent, activation of Fas/Fas-ligand system could still be involved in the induction of apoptosis in erythema multiforme.

Oral pemphigus vulgaris: an immunofluorescent study of fifty-eight cases.

Oral mucosa biopsy specimens and sera from fifty-eight patients with pemphigus vulgaris limited to the oral cavity were studied by the direct and indirect immunofluorescence technique. Direct immunofluorescence demonstrated intercellular substance (ICS) deposition of IgG, either alone or in combination with C3, IgA, and IgM, in fifty-seven out of fifty-eight (98.3 per cent) oral mucosa biopsy specimens examined. At the time of initial evaluation circulating ICS antibodies were detected in twenty-eight out of fifty-eight patients (48.3 per cent) when a compound animal epithelial tissue was used as substrate. However, when normal human oral mucosa was used as substrate, circulating ICS antibodies were observed in fifty out of fifty-eight patients (86.2 per cent). It is concluded that direct and indirect immunofluorescence is a valuable diagnostic test in the early diagnosis of oral pemphigus vulgaris. In addition, normal human oral mucosa is a more appropriate substrate than animal epithelial tissue.

Cicatricial pemphigoid: Direct and indirect immunofluorescent studies

Oral mucosa, skin tissue, and serum samples from thirty-three patients with cicatricial pemphigoid were studied by the direct and indirect immunofluorescent techniques to determine the presence of tissue-bound and circulating antibodies. A linear continuous basement membrane zone pattern was observed in 96.9 percent of the oral mucosa biopsy specimens studied. This pattern is indistinguishable from the pattern observed in bullous pemphigoid. In 97 percent of the cases clinically healthy skin biopsy specimens were negative for basement membrane zone staining. Circulating anti-basement membrane zone antibodies were present in 36.4 percent of thirty-three patients with cicatricial pemphigoid in low titer (1:10 to 1:40), when normal oral mucosa was used as substrate. The demonstration of tissue-bound and circulating basement membrane zone antibodies in cicatricial pemphigoid morphologically identical to those found in bullous pemphigoid provides further support for the concept that the two diseases may represent variants of the same entity.