Analysis of chromosome 9p21 deletion and p16 gene mutation in salivary gland carcinomas

Cerilli, Lisa A.; Swartzbaugh, Joanna R; Saadut, Rega; Marshall, Carina E.; Rumpel, Craig A.; Moskaluk, Christopher A.; Frierson, Henry F.

doi:10.1016/s0046-8177(99)90044-8

Cited by 50 publications

(38 citation statements)

References 12 publications

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“…[32][33][34] In our study, p16 could not be linked to tumor progression, as it has been suggested previously by others. [32][33][34] We could only detect a p16 mutation in 1 of 34 tumor specimens (2.9%), a percentage that is lower than that described by Cerilli et al 35 (7 of 9 tumor specimens [77.8%]). Mutations were detected exclusively in exon 2 only in (ϩ) and (ϩϩ)-positive p16 samples.…”

Section: Table 4 Prognostically Significant Factors In Sdc Clinical Ccontrasting

confidence: 70%

Clinical and immunohistologic typing of salivary duct carcinoma

Jaehne

Roeser

Jaekel

et al. 2005

Cancer

295

346

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BACKGROUNDDue to the low incidence of salivary duct carcinoma (SDC), only limited data in regard to the biologic behavior of this tumor and its immunohistochemical characteristics are available. The authors analyzed the clinical, molecular, and genetic profile of SDC and identified prognostic factors.METHODSThe follow‐up of 50 patients with SDC was obtained and paraffin‐embedded tumor samples were examined immunohistochemically. In all samples, the expression of Ki‐67, HER‐2, and the oncoproteins p16 and p53 was examined immunohistochemically, followed by a mutation analysis of p16 and p53. The survival rate was calculated by the Kaplan–Meier method and prognostic variables were analyzed with the log‐rank test.RESULTSSDC predominantly effected male patients (66%) in their 7th decade of life. SDC mainly occurred in the parotid gland (78%; submandibular gland, 12%; minor salivary glands, 10%). Approximately two‐thirds of the patients (33 of 50) presented with a T3/T4 tumor. In 28 patients (56%), cervical lymph node metastasis was present at the time of diagnosis. Local disease recurrence was observed in 48% of patients an average of 17.4 months after initial treatment. Distant disease metastasis developed in 48% of patients an average of 29 months after initial treatment. The average overall survival period was 56.2 months. In the current study, 20.6% of the probes with positive HER‐2/neu expression were (+++) positive. p53 was expressed in 83.9% of the tumor samples. In 11.8% of the tumor samples, there was a lack of p16 expression.CONCLUSIONSMutations of the p53 gene were more frequent in tumor samples with (++) and (+++) immunoreactivity and mainly affected exons 7 and 8. A mutation of the p16 gene was only found in 1 tumor sample. Expression of HER‐2/neu and p53 was statistically linked (P < 0.05) to early local disease recurrence, distant disease metastasis, and survival rates. Cancer 2005. © 2005 American Cancer Society.

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Section: Table 4 Prognostically Significant Factors In Sdc Clinical Ccontrasting

confidence: 70%

Clinical and immunohistologic typing of salivary duct carcinoma

Jaehne

Roeser

Jaekel

et al. 2005

Cancer

295

346

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“…This is consistent with a previous survey of mammary tumor phenotypes in MMTV-Ras, MMTVMyc, and/or MMTV-Neu transgenic mice, where tumor morphology was closely correlated with the activated oncogene expressed (Cardiff et al, 1991). Accumulating cytogenetic and molecular biologic data indicate that specific human salivary tumors are often associated with predictable molecular perturbations (reviewed in Cerilli et al, 1999;El-Naggar et al, 1997;Johns et al, 1996;Sandros et al, 1990).…”

Section: Dardick Et Almentioning

confidence: 99%

Submandibular Gland Adenocarcinoma of Intercalated Duct Origin in Smgb-Tag Mice

Dardick

Paulus

et al. 2000

Laboratory Investigation

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SUMMARY:A line of transgenic mice that develops submandibular gland adenocarcinoma of intercalated duct origin was established. In these mice, the oncogene SV40 T antigen (Tag) is expressed from the neonatal submandibular gland secretory protein b (Smgb) gene promoter. This hybrid gene directs expression of the oncoprotein to neonatal submandibular gland proacinar and terminal tubule cells and to intercalated ducts of the adult gland. Transgene expression resulted in duct luminal cell hyperplasia as early as 20 to 30 days postnatally, which progressed to dysplasia by 3 to 4 months of age. Marked dysplasia and in situ carcinoma were evident at 4 to 6 months of age. All histologic changes were more pronounced in males. Submandibular gland adenocarcinoma developed stochastically in more than half of the adult male mice by 12 months of age (average age: 10.8 months, range: 6 to 13.5 months). Tag expression persisted in in situ carcinoma and all tumors. Using a combination of immunocytochemical and ultrastructural criteria, submandibular gland dysplasia and tumors were found to originate from intercalated ducts. The dysplastic ducts and adenocarcinoma in Smgb-Tag mice were morphologically similar to previously reported Tag-induced dysplasias of striated ducts and granular convoluted tubules and a Tag-induced adenocarcinoma of striated duct origin. These findings demonstrate that salivary gland dysplasias and tumors of similar histologic appearance can arise from distinct differentiated cell types. Analysis of the molecular changes accompanying tumor formation in Smgb-Tag mice could increase knowledge of human salivary gland tumorigenesis. (Lab Invest 2000, 80:1657-1670.

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“…The Rb susceptibility gene RB-1 encodes a protein that regulates the transition from G1 phase to S phase of the cell cycle [25,48]. The tumor suppressor gene p16 is believed to encode a negative regulatory protein that controls the progression of eucaryotic cells through G1 phase of the cell cycle by interacting with CDK4 and inhibiting its kinase activity [6]. In the absence of a functional p16 protein, CDK4 binds to cyclin D and phosphorylates Rb, which stimulates entry of the cell into S phase [38].…”

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confidence: 99%

The Significance of p53 and Retinoblastoma Pathways in Canine Hemangiosarcoma

Yonemaru

Sakai

Murakami

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. To investigate whether inactivation of the p53 and retinoblastoma (Rb) protein pathways contributes to the development of canine hemangiosarcoma (HSA), we examined immunohistochemically the expression of p53, Rb, phosphorylated Rb (phospho-Rb), p16, and cyclin D1 in 39 spontaneous canine HSAs and 10 hemangiomas. In addition, mutations in the p53 gene were analyzed by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and PCR direct sequencing; furthermore, we quantified cyclin D1 mRNA by semiquantitative real-time reverse transcription-PCR. Positive immunoreactivity for p53 was observed in 17.9% of HSAs. However, mutations were not detected in these cases. The labeling indices for Rb, phospho-Rb, and cyclin D1 were markedly higher in all HSAs than in hemangiomas. Of the 7 cases with cyclin D1-positive immunoreactivity, 4 overexpressed cyclin D1 mRNA (to a level more than 10-fold higher than that of GAPDH mRNA). The p16 protein was clearly detected in all hemangiomas; however, 82% of the neoplastic cells in HSA showed a loss of or low immunoreactivity. These results suggest that alteration of the p16-cyclin D1-Rb pathway, rather than the p53 pathway, may be associated with the pathogenesis of canine HSA. KEY WORDS: canine hemangiosarcoma, cyclin D1, p16, p53, Rb.

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Analysis of chromosome 9p21 deletion and p16 gene mutation in salivary gland carcinomas

Cited by 50 publications

References 12 publications

Clinical and immunohistologic typing of salivary duct carcinoma

Clinical and immunohistologic typing of salivary duct carcinoma

Submandibular Gland Adenocarcinoma of Intercalated Duct Origin in Smgb-Tag Mice

The Significance of p53 and Retinoblastoma Pathways in Canine Hemangiosarcoma

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