Detection of human papillomavirus DNA sequences in oral squamous cell carcinomas and their relation to p53 and proliferating cell nuclear antigen expression

BACKGROUND: The etiology of oral squamous cell carcinoma (SCC) is still obscure. Since human papillomavirus (HPV) DNAs are associated with carcinoma of the uterine cervix, carcinomas of the oral cavity were investigated to ascertain if these viruses are present in squamous carcinomas of this anatomic site. METHODS: Seventy-seven oral mucosal SCCs were examined for the presence of HPV DNAs by polymerase chain reaction and dot blot hybridization. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and p53 was performed and single strand conformation polymorphism analysis for p53 was undertaken. In situ hybridization detection of HPV-16 DNA also was performed. RESULTS: Human papillomavirus-16 DNA was detected in 23 cases of oral SCC and both HPV-16 and HPV-18 DNA were detected in one case of tongue SCC. Human papillomavirus DNAs were detected of 11 of 33 tongue, 4 of 15 gingival, 2 of 4 palate, 2 of 5 buccal mucosa, 3 of 7 maxillary sinus, and 2 of 11 the floor of the mouth SCCs. None were detected in SCCs of the retromolar region (0/2). Immunohistochemical examination for p53 was performed in 26 cases of oral SCC and the accumulation of p53 protein was observed in 6 cases (i.e., in 4 of 17 HPV DNA-negative cases and in 2 of 9 HPV DNA-positive cases). Single strand conformation polymorphism analysis confirmed gene mutations in all 6 cases. Human papillomavirus-16 DNA was predominantly identified in cancer cells that showed a morphologic resemblance to basal cells and its hybridized signal in keratinized cells was reduced by in situ hybridization detection. Immunohistochemical detection of PCNA revealed its cooccurrence with HPV-16 DNA in cancer cells. CONCLUSIONS: These results suggest that HPV-16 DNA sequences may have the capability to maintain the proliferative state of epithelial cells, and may contribute to the production of malignant phenotypes.     

Detection of human papillomavirus DNA in laryngeal squamous cell carcinoma by polymerase chain reaction

Although human papillomaviruses (HPVs) have been found in many, but not all, tumours of the oral cavity, nose, pharynx and larynx, the true role of HPV in malignant tumours of the head and neck is still unclear. The presence of HPV DNA was investigated in 45 fresh squamous cell carcinoma (SCC) specimens and in 29 normal mucosa specimens collected from 45 primary laryngeal SCC patients. HPV DNA was detected using the polymerase chain reaction (PCR) with consensus primers that detect HPV types 6, 11, 16 and 18.9 of the 45 patients (20%) were HPV positive; the presence of HPV was also detected in the corresponding normal laryngeal mucosa of four of the 29 specimens (14%). No statistically significant differences were found between the presence of HPV DNA in normal specimens and in neoplastic mucosa specimens. No correlation was found between HPV DNA positive tumours and size, T classification, lymph node involvement and histological grading. This study adds further evidence suggesting a possible role of HPV DNA infection in laryngeal carcinogenesis.     

Papillary squamous cell carcinoma of the uterine cervix: report of a case with HPV 16 DNA and brief review

Papillary squamous cell carcinoma (PSCC) of the uterine cervix is a rare variant of squamous cell carcinoma (SCC). It is characterized by a papillary architecture and markedly atypical epithelium. Invasion and metastasis have been reported. We report a case of PSCC in a 72-year-old woman who subsequently tested positive for HPV 16. To our knowledge, this is the first report of HPV typing in a case of PSCC. Our finding of a high-risk HPV type in PSCC may help explain why PSCC has been reported to have a clinical course similar to that of nonpapillary SCC.     

Mutations of K-ras oncogene and absence of H-ras mutations in squamous cell carcinomas of the lung

Mutations of the K-ras gene have been implicated in the pathogenesis of human lung adenocarcinomas. In most studies published so far, squamous cell lung cancers harbored ras mutations only exceptionally or no mutations were detected at all. We have examined 141 lung tumor DNA samples for mutations in codons 12, 13, and 61 of K-ras and H-ras oncogenes. A large panel of 118 squamous cell carcinomas was included in the study. For K-ras codon 12, we used a sensitive two-step PCR-restriction fragment length polymorphism method which detects <1% of mutated DNA in the sample. K-ras mutations were found in 17 tumors (12%; 14 in codon 12 and 3 in codon 13). Among 19 adenocarcinomas, mutation was revealed in 7 samples (37%). Of these, one sample harbored two point mutations in codon 12. Nine mutational events were found in squamous cell carcinomas (8%, one adenosquamous carcinoma included, all in codon 12). Of four large cell carcinomas, one contained a mutation. Mutant-enriched PCR products harboring mutations were directly sequenced. Fifteen mutational events were G-->T transversions or G-->A transitions, one was a G-->C transition, and one sample revealed a frameshift deletion of one G from codon 12. Similar mutational spectrum was found in both squamous cell carcinomas and adenocarcinomas, suggesting similar carcinogenic pathways in both histological types of the tumor. The presence of mutations did not correlate with the stage of the disease. Moreover, we analyzed all samples for mutations in codons 12, 13, and 61 of the H-ras gene. We found only one mutation in codon 12. Thus, H-ras mutations apparently play an inferior role in lung carcinogenesis. We conclude that mutations of the K-ras oncogene can play a role in the development of not only lung adenocarcinomas but also of a subset (about 8%) of squamous cell carcinomas.     

Relationship between human papillomavirus E7 protein and Rb gene product in fresh tissues of squamous cervical carcinoma

OBJECTIVE: To study the possibility of complex formation of the E7 protein encoded by human papillomavirus (HPV) binding to retinoblastoma gene product (pRb) in fresh samples of squamous cervical carcinoma (SCC). METHODS: HPV 6/11, 16, 18, 33 DNA were detected in 40 samples of by polymerase chain reaction technique (PCR). The complexes of HPV E7-pRb were examined in fresh tissues of HPV contained SCC through capture enzyme linked immunosorbent assay (capture-ELISA). RESULTS: 45.0% (18/40) of the samples were proved to be HPV positive by PCR. Out of 18 samples with HPV positive samples, the complexes of HPV E7-pRb were detected in 9 cses, including 1 HPV18 positive and 8 HPV16 positives. The complexes of HPV E7-pRb were not found in 2 cases of positive HPV 6/11. No correlation was observed between the E7 protein binding to pRb and the histological grade of cervical carcinoma (P < 0.05). There was correlation with clinical staging, the number of cases showing that the E7 protein pRb complex in stage I was significantly higher than that in stages II-IV (P < 0.05). CONCLUSIONS: The complex of "high risk" HPV E7-pRb was demonstrated in fresh tissues of SCC. There is no correlation between the complex and histological grade of SCC. The complex formation may occur in the early developmental stage of cervical cancer.     

P53 in squamous metaplasia: a marker for risk of respiratory tract carcinoma

Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl-2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stained nuclei were counted. Normal bronchial epithelium obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43%). The positive predictive values of p53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 80%, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor the mitotic index distinguished patient groups with and without carcinoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.     

Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix

Expression of squamous cell carcinoma (SCC) antigen emerged concurrently with squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium. SCC antigen expression differed considerably among the histomorphologic cell types of cervical carcinoma. Large cell nonkeratinizing carcinoma contained high levels of the antigen. In contrast, no appreciable expression of SCC antigen was observed in small cell nonkeratinizing carcinoma. The pattern of SCC antigen expression closely coincided with EGF receptor (EGF-R) expression in cervical squamous neoplasia. This suggests that the expression of SCC and EGF-R in cervical carcinoma is related to the differentiation or dedifferentiation processes of the tumor cells. SCC production by CaSki cervical epidermoid carcinoma cells was stimulated by EGF. It seems likely that an autocrine system, in which EGF serves as the signal, may exist in cervical squamous carcinoma. 17beta-estradiol and L-triiodothyronine were found to upregulate EGF-R expression, proliferative potential and SCC production in the CaSki cervical carcinoma cells.     

Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival

Recent studies have shown that p53 mutations are frequently found in cancer of the head and neck, whereas others have indicated that human papilloma virus (HPV) infection may be involved. Thus far, no studies have examined both p53 and HPV in the same patient population and correlated the results with clinical characteristics and outcome. The purpose of this study was to examine any interrelationship between p53 and HPV in patients with squamous cell carcinoma (SCC) of the head and neck. We also planned to correlate the experimental findings with clinical characteristics, known risk factors, and treatment outcome to determine whether any prognostic factors could be detected. Archival material from 66 patients with SCC of the head and neck were selected for study based on the availability of tissue from the primary tumors prior to treatment. A data base was constructed containing all clinical parameters at the time of diagnosis and risk factors. Genomic DNA was isolated and amplified using PCR, followed by SSCP analysis and direct genomic sequencing of all variants to detect p53 mutations. Two independent methods were used for HPV detection: (a) PCR amplification using primers homologous to the E6 region of HPV 16, 18, and 33, followed by RFLP analysis; and (b) PCR amplification with HPV L1 consensus primers, followed by triple restriction enzyme digestion. The results were entered into the data base for statistical analysis. Twenty-four percent of patients were found to have p53 mutations, and 18% were positive for HPV infection. Only one patient was positive for both. Tonsilar cancer was strongly correlated with HPV (P = 0.0001) and inversely correlated with p53 (P = 0.03). The only clinical parameter associated with p53 mutation was a trend toward a heavier smoking history. A subset analysis of the patients with tonsilar cancer revealed inverse correlations with smoking (P = 0. 015) and alcohol use (P = 0.05). Also, white patients with SCC of the tonsil were more likely to be HPV positive (P = 0.015). No significant relationships with outcome were detected with either p53 or HPV in the entire population. A subset analysis of patients with stage IV disease revealed that HPV infection was correlated with overall survival. This is the largest study to date to examine both p53 and HPV in patients with SCC of the head and neck. Our results suggest that HPV may be involved in the development of these cancers in patients without traditional risk factors and that HPV-related cancers are more prevalent in the white race.     

Carcinomas of Bartholin''s gland. Histogenesis and the etiological role of human papillomavirus

In this study, we examine 10 primary carcinomas of Bartholin's gland, including seven squamous carcinomas, two adenoid cystic carcinomas, and one adenocarcinoma, as well as four non-neoplastic Bartholin's gland. Six of seven squamous cell carcinomas contained human papillomavirus (HPV) type 16 DNA detectable by the polymerase chain reaction; one of these demonstrated HPV type 16 by in situ hybridization. The two adenoid cystic carcinomas, the adenocarcinoma, and the non-neoplastic Bartholin's gland epithelium showed no evidence of HPV DNA by polymerase chain reaction or in situ hybridization. A panel of eight antibodies (Cam 5.2, B72.3, CEA, EMA, MCA, Lewis X, ER, and PR) demonstrate that the squamous, transition zone, duct, acinar, and myoepithelial cells or Bartholin's gland are antigenically distinct, and are similar to those reported in analogous areas of the uterine cervix. Squamous carcinoma and adenocarcinomas of Bartholin's gland are antigenically similar, and seem to arise from the transition zone of the Bartholin's gland duct. The origin of adenoid cystic carcinomas is more difficult to determine; it is distinct from squamous and adenocarcinomas and seems more likely to arise from myoepithelial cells. We conclude that adenocarcinoma and squamous cell carcinoma of Bartholin's gland arise in the transition zone of Bartholin's gland, which is similar to the transition zone of the uterine cervix. We also show that HPV is associated with Bartholin's gland carcinoma and may play a role in the genesis of malignancy.     

Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ

A case of small-cell neuroendocrine carcinoma of the uterine cervix associated with squamous cell carcinoma and adenocarcinoma in situ is reported. The tumor consisted mainly of uniform small cells with a population of intermediate cells that resembled carcinoid tumor cells. Foci of micro-invasive squamous cell carcinoma and adenocarcinoma in situ were recognized separately, adjacent to the main tumor. Both Grimelius stain and immunostaining of serotonin were positive for small-cell and intermediate-cell carcinoma. Neurosecretory granules were demonstrated by electron microscopy. Microacini with positive mucin staining and microvilli-like structures suggested glandular or exocrine differentiation of the tumor. Three distinctive types of differentiation, neuroendocrine, exocrine and squamous characteristics, were expressed in the tumor.     

Genomic imprinting in the brain

Biopsies of cervix uteri from 166 patients with benign and malignant lesions (12 normal, 48 inflammatory lesion, 6 adenocarcinoma, 2 adenosquamous carcinoma and 98 from squamous cell carcinomas) were studied histochemically. The stains used were PAS with/without diastase, AB/PAS (pH 2.5) and OR/AB. In inflammatory lesions neutral mucin was predominent which was replaced by sialomucin and sulphomucin in endocervical polyps. In malignant lesions sulphomucin was predominent. Seventeen percent cases of squamous cell carcinomas needed reclassification after mucin staining. Of the fourteen large cell non-keratinizing squamous cell carcinomas, 12 were reclassified as squamous cell carcinoma with mucin secretion and 2 as adenosquamous carcinoma. One case of small cell non-keratinizing squamous cell carcinoma was reclassified as moderately differentiated adenocarcinoma. None of the keratinizing carcinomas had evidence of mucin secretion. Mucin histochemistry should be done routinely on non-keratinizing squamous cell carcinomas to pick up more cases of carcinoma with evidence of mucin secretion which can be missed on routine haematoxylin and eosin stains. Such carcinomas are known to pursue a more aggressive clinical course and have a poorer prognosis than non-mucin secreting type of squamous cell carcinoma.     

Mucoepidermoid carcinoma of the pancreas: report of a case

We present herein the case of a 64-year-old man diagnosed as having a mucoepidermoid carcinoma of the pancreas. The tumor originated in the tail of the pancreas and invaded the spleen, left adrenal gland, left kidney, and transverse colon. Liver and peritoneal metastases were also noted. Despite surgical treatment and adjuvant chemotherapy, the disease progressed rapidly and the patient died of cachexia 4 months after his initial diagnosis. Mucoepidermoid carcinoma of the pancreas is a rare entity, and is believed to be a form of adenosquamous carcinoma known as adenoacanthoma. However, in this patient, no differentiated squamous cell component could be detected. In fact, the tumor was composed of mucin-producing cells, epidermoid cells, and intermediate cells. Immunohistochemical staining for the carcinoembryonic antigen, CA19-9, and SPan-1 demonstrated a production of cancerous mucin in the epidermoid cells, suggesting that mucoepidermoid carcinoma may arise from the squamoid metaplasia of an adenocarcinoma.     

Early acquisition of homozygous deletions of p16/p19 during squamous cell carcinogenesis and genetic mosaicism in bladder cancer

We looked for p16/p19 deletion and p16 promoter methylation, as well as loss of 9p21 heterozygosity in pure squamous cell carcinomas (SCC), and in transitional cell carcinomas (TCC) of the bladder with SCC components. Homozygous deletion of p16/p19 was detected in 11 of 21 (52%) cases of pure SCCs and in three of ten (30%) cases of TCC with SCC. Three cases of TCC with SCC had p16/p19 deletion, hypermethylation of the p16 promoter, or LOH on 9p21 only in the SCC components, suggesting that these molecular alterations occurred preferentially in SCC. Interestingly, homozygous deletion of p16/p19 was observed in squamous metaplasia from bladder cancer patients (five of 11, 45%), showing that this change occurred in preneoplastic cells. On the other hand, p16/p19 deletions were not found in squamous metaplasias from non cancerous patients. Hypermethylation of the p16 promoter was observed in two of 14 tumors (14%) and none of seven metaplasias examined. These data suggest that: (a) p16/p19 deletion is associated with early carcinogenesis of SCC of the bladder, and squamous metaplasia of the bladder cancer patient has already sustained genetic changes found in cancer, and (b) genetic mosaicism occurs in cases of TCC with SCC, with the SCC component showing more frequent 9p21 alterations than the TCC component.     

Expression of CD44 standard and CD44 variant 6 in human lung cancer

We immunohistochemically examined the expression of CD44 standard (CD44 st) and CD44 variant 6 (CD44 v6) in 112 cases of primary lung cancer, and their relationship to the clinical milieu, including the clinical stage. In 46 cases of squamous cell carcinoma, expression of CD44 st was observed in 45.7% of the cases, and expression of CD44 v6 was observed in 60.9%. In 43 cases of adenocarcinoma, positive staining of CD44 st and CD44 v6 was seen in 2.3% and 4.7% of the cases, respectively. None of 21 small cell carcinomas was positive for CD44 st or CD44 v6. In squamous cell carcinomas, the expression of CD44 st and CD44 v6 was observed at a rate significantly higher than in other histologic type. Most specimens positive for CD44 st stained positively for CD44 v6. Therefore, it seems likely that the CD44 expression observed in squamous cell carcinoma of the lung was a variant CD44 containing the domain encoded by variant exon 6. The expression of CD44 v6 was not related to the clinical stage. Significant association between CD44 v6 and differentiation of squamous cell carcinoma was seen; 2/7 (28.6%) for poorly differentiated, 19/31 (61.3%) for moderately differentiated, and 7/8 (87.5%) for well differentiated squamous cell carcinomas (p = 0.02 by trend test). It was previously reported that CD44 st and CD44 v6 were expressed in both normal bronchial epithelium and squamous cell metaplasia. These results suggest that the expression of CD44 v6 in squamous cell carcinoma of the lung may reflect the immunohistochemical characteristics of the tissue from which such carcinoma emerge.     

CYFRA 21-1 is a useful marker for esophageal squamous cell carcinoma

BACKGROUND: CYFRA 21-1 measures soluble cytokeratin-19 fragments in serum and is a useful marker for lung carcinoma, especially squamous cell carcinoma (SCC). The authors conducted this study to determine the significance of CYFRA 21-1 in patients with esophageal SCC. METHODS: Expression and production of cytokeratin-19 in the authors' six established esophageal SCC cell lines were determined by immunocytochemical staining and enzyme-linked immunoadsorbent assay, respectively. The correlation between serum CYFRA 21-1 levels and expression of cytokeratin-19 in human tumors was investigated by immunohistochemical staining. The correlation between serum CYFRA 21-1 levels and clinicopathologic factors was examined in 48 patients with esophageal SCC, as were SCC antigen and carcinoembryonic antigen (CEA). RESULTS: Of the 6 cell lines, 5 lines expressed cytokeratin-19 in their cytoplasm and produced soluble cytokeratin-19 fragments. Twenty-three of 48 patients had elevated CYFRA 21-1 levels (>3.5 ng/mL), whereas none of the reference group (consisting of healthy volunteers or patients with benign disease) showed positive levels. The specificity, sensitivity, and accuracy of CYFRA 21-1 were 100%, 47.9%, and 66.7%, respectively. CYFRA 21-1 showed significantly higher sensitivity and accuracy than SCC antigen or CEA (P < 0.05). Univariate analysis revealed that CYFRA 21-1 levels correlated with disease progression (including tumor size, tumor depth, and pTNM stage), resectability, and curability. There was a significant association between the level of CYFRA 21-1 and its intensity of immunohistochemical staining in vitro as well as in vivo. CONCLUSIONS: CYFRA 21-1 appears to be a useful marker for human squamous cell carcinoma of the esophagus.     

Nitric oxide synthase activity in human lung cancer

Nitric oxide synthases (NOS) exist in human tumor cell lines and solid tumor tissues, and it has been suggested that NO may play important roles in growth, progression or metastasis of tumors. We investigated the activity and distribution of NOS in a series of human cancer and normal lung tissues. Seventy-two primary lung cancer samples (44 cases of adenocarcinoma, 18 of squamous cell carcinoma, 4 of large cell carcinoma, 2 of small cell carcinoma, 2 of adenosquamous carcinoma, and 2 of carcinoids) and corresponding normal lung samples were obtained from surgically treated patients. In normal lung tissues, little NOS activity was observed with no correlation between the patient's age and NOS activity. The total NOS activities in lung adenocarcinoma samples were significantly higher than those in other types of lung cancers of normal lung samples (P < 0.05). Analysis by tumor grade of the adenocarcinoma samples revealed no significant difference of NOS activity between grades. TNM classification showed that, although T stage did not correlate with NOS activity, cancer tissues from patients with N2 disease tended to have lower activity than those from patients with NO or N1 disease. Immunohistochemical studies revealed that the intensity of NOS immunoreactivity correlated with NOS activity. These results suggest that NO may play an important role in the metabolism and behavior of lung cancers, especially adenocarcinoma.     

Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract. METHODS: In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus. RESULTS: Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found. CONCLUSIONS: BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.     

Relationship of p53 overexpression to other cell cycle regulatory proteins in oral squamous cell carcinoma

Aberrations of the p53 gene and the overexpression of its protein are described in a variety of neoplasms, including oral and other head and neck cancers. Here we report the association of p53 (over)expression with a downstream cell cycle inhibitor p21/waf 1 in oral squamous cell carcinoma (SCC). The loss of expression of p16 and p27, two other cyclin-dependent kinase (cdk) inhibitors, was also examined. In this panel of tumours, 10/24 carcinomas were p53-immunopositive. Heterogeneous expression of p21 and p27 was seen in 10/24 SCC and 9/16 SCC, respectively, and this was not correlated to p53 status. The expression of p21 and p27 in these SCCs suggests the existence of mechanisms by which some growing tumour cells may tolerate these cell cycle inhibitors; eight SCCs lacked expression of both inhibitors but only two of these cancers overexpressed p53, suggesting that accumulation of p21/p27 can be independent of the functional status of the p53 gene. Data do not support a clear example of a phenotype that shows an overexpression of p53 with downregulation of p21 or p27 leading to cell cycle alterations. Furthermore, only three SCCs were p16-negative and p53-positive. This suggests that these two tumour suppressors may act in separate pathways.     

Expression of p53 protein correlates with decreased survival in patients with areca quid chewing and smoking-associated oral squamous cell carcinomas in Taiwan

Expression of p53 protein was examined in oral squamous cell carcinoma (SCC) from patients who were areca quid (AQ) chewers and/or tobacco smokers, using anti-p53 antibodies with an immunoperoxidase technique. Positive p53 stain was observed in 47 of 81 (58%) cases of oral SCC. p53 overexpression was found to be higher in patients without AQ chewing and smoking habits than in patients with these two habits (80% vs 52%, P=0.076). No significant correlation was found between p53 expression and the patients' age, sex, cancer location, clinical staging, primary tumor TNM status, or histological differentiation of SCC. The Kaplan-Meier analysis showed that the prognosis for patients with p53-negative tumors was significantly better than that for patients with p53-positive tumors (P<0.05). A significant correlation was also observed between positive lymph node status and poor prognosis (P<0.05). These results suggest that p53 may serve as an adjuvant marker of poor survival in patients with oral SCCs in Taiwan.