Overexpression of CyclinD1 and Underexpression of P16 Correlate with Lymph Node Metastases in Laryngeal Squamous Cell Carcinoma in Chinese Patients

Overview

Journal Clin Exp Metastasis

Specialty Oncology

Date 2008 Sep 13

PMID 18787961

Citations 16

Authors

Zhi-Jie Fu

Zhi-Yong Ma

Qi-Rong Wang

Da-Peng Lei

Rong Wang

Chun-Xi Liu

Xin-Liang Pan

Affiliations

Soon will be listed here.

Abstract

Background: CyclinD1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorgenesis of laryngeal squamous cell carcinoma (LSCC). Previous studies have examined the level of expression of cyclinD1 or p16 in LSCC but no such information is available for their relation and their correlation with lymph node metastasis in Chinese patients.

Patients And Methods: A total of 58 patients underwent surgical resection of laryngeal tumours in the Department of Otolaryngology, Qilu Hospital Shandong University between January 2001 and December 2002. All pathologic specimens were available for immunohistochemical study using antibodies against cyclinD1 and p16.

Results: Compared with normal epithelium, expression of CyclinD1 in the LSCC was significantly higher (62.1% vs. 10.0%, P < 0.05), expression of p16 was significantly lower (48.3% vs. 90.0%, P < 0.05); CyclinD1 expression in LSCC was up-regulated in TNM classification (r (s) = 0.409, P < 0.05) as well as with cervical lymph node metastases (r (s) = 0.294, P < 0.05); p16 expression in LSCC was down-regulated with cervical lymph node metastases (r (s) = -0.275, P < 0.05); negative significant correlation between p16 immunostaining and CyclinD1 was observed in LSCC (r (s) = -0.331, P < 0.05).

Conclusion: There was a negative correlation between CyclinD1 expression and p16 expression in LSCC. The over-expression of CyclinD1 and the under-expression of p16 may play a significant role in the incidence and development of LSCC and may be important indicators for cervical lymph node metastases in Chinese patients of LSCC.

Citing Articles

p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?.

Gallus R, Rizzo D, Rossi G, Mureddu L, Galli J, Artuso A Pathogens. 2024; 13(2).

PMID: 38392838 PMC: 10892421. DOI: 10.3390/pathogens13020100.

Pancancer survival analysis of cancer hallmark genes.

Nagy A, Munkacsy G, Gyorffy B Sci Rep. 2021; 11(1):6047.

PMID: 33723286 PMC: 7961001. DOI: 10.1038/s41598-021-84787-5.

Distinct Biomarker Profiles and Clinical Characteristics in T1-T2 Glottic and Supraglottic Carcinomas.

Wachters J, Kop E, Slagter-Menkema L, Mastik M, van der Wal J, van der Vegt B Laryngoscope. 2020; 130(12):2825-2832.

PMID: 32065407 PMC: 7754398. DOI: 10.1002/lary.28532.

Upregulated TRPC5 plays an important role in development of nasal polyps by activating eosinophilic inflammation and NF-κB signaling pathways.

Fu Z, Gu L, Li N, Ma Z, Ling M, Wang Y Int J Clin Exp Pathol. 2020; 11(4):1935-1945.

PMID: 31938299 PMC: 6958183.

Prognostic impact of high p16/cyclin D1 index in breast cancer.

Kim G, Kim D, Min K, Kim S Int J Clin Exp Pathol. 2020; 12(6):2224-2232.

PMID: 31934045 PMC: 6949626.

References

Greenlee R, Murray T, Thun M . Cancer statistics, 2001. CA Cancer J Clin. 2001; 51(1):15-36. DOI: 10.3322/canjclin.51.1.15. View

Dong Y, Sui L, Sugimoto K, Tai Y, Tokuda M . Cyclin D1-CDK4 complex, a possible critical factor for cell proliferation and prognosis in laryngeal squamous cell carcinomas. Int J Cancer. 2001; 95(4):209-15. DOI: 10.1002/1097-0215(20010720)95:4<209::aid-ijc1036>3.0.co;2-r. View

Jares P, Fernandez P, Campo E, Nadal A, Bosch F, Aiza G . PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas. Cancer Res. 1994; 54(17):4813-7. View

Sherr C, Roberts J . CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999; 13(12):1501-12. DOI: 10.1101/gad.13.12.1501. View

Weinberg R . The retinoblastoma protein and cell cycle control. Cell. 1995; 81(3):323-30. DOI: 10.1016/0092-8674(95)90385-2. View

Kamb A, Gruis N, Liu Q, Harshman K, Tavtigian S, STOCKERT E . A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994; 264(5157):436-40. DOI: 10.1126/science.8153634. View

Takes R, Baatenburg de Jong R, Schuuring E, Hermans J, Vis A, Litvinov S . Markers for assessment of nodal metastasis in laryngeal carcinoma. Arch Otolaryngol Head Neck Surg. 1997; 123(4):412-9. DOI: 10.1001/archotol.1997.01900040048008. View

Krecicki T, Smigiel R, Fraczek M, Kowalczyk M, Sasiadek M . Studies of the cell cycle regulatory proteins P16, cyclin D1 and retinoblastoma protein in laryngeal carcinoma tissue. J Laryngol Otol. 2004; 118(9):676-80. DOI: 10.1258/0022215042244769. View

Takeuchi H, Ozawa S, Ando N, Shih C, Koyanagi K, Ueda M . Altered p16/MTS1/CDKN2 and cyclin D1/PRAD-1 gene expression is associated with the prognosis of squamous cell carcinoma of the esophagus. Clin Cancer Res. 1998; 3(12 Pt 1):2229-36. View

10.

Lin H, Berry G, Sun Z, Fee Jr W . Cyclin D1 and p16 expression in recurrent nasopharyngeal carcinoma. World J Surg Oncol. 2006; 4:62. PMC: 1569377. DOI: 10.1186/1477-7819-4-62. View

11.

Capaccio P, Pruneri G, Carboni N, Pagliari A, Buffa R, Neri A . Cyclin D1 protein expression is related to clinical progression in laryngeal squamous cell carcinomas. J Laryngol Otol. 1997; 111(7):622-6. DOI: 10.1017/s0022215100138149. View

12.

Gallo O, Santucci M, Franchi A . Cumulative prognostic value of p16/CDKN2 and p53 oncoprotein expression in premalignant laryngeal lesions. J Natl Cancer Inst. 1997; 89(15):1161-3. DOI: 10.1093/jnci/89.15.1161. View

13.

Cattaruzza M, Maisonneuve P, Boyle P . Epidemiology of laryngeal cancer. Eur J Cancer B Oral Oncol. 1996; 32B(5):293-305. DOI: 10.1016/0964-1955(96)00002-4. View

14.

El-Naggar A, Lai S, Clayman G, Zhou J, Tucker S, Myers J . Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications. Hum Pathol. 1999; 30(9):1013-8. DOI: 10.1016/s0046-8177(99)90217-4. View

15.

Serrano M, Hannon G, Beach D . A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993; 366(6456):704-7. DOI: 10.1038/366704a0. View

16.

Bartkova J, Lukas J, Strauss M, Bartek J . Cyclin D1 oncoprotein aberrantly accumulates in malignancies of diverse histogenesis. Oncogene. 1995; 10(4):775-8. View

17.

Forastiere A, Koch W, Trotti A, Sidransky D . Head and neck cancer. N Engl J Med. 2002; 345(26):1890-900. DOI: 10.1056/NEJMra001375. View

18.

Lai S, El-Naggar A . Differential expression of key cell cycle genes (p16/cyclin D1/pRb) in head and neck squamous carcinomas. Lab Invest. 1999; 79(3):255-60. View

19.

Pignataro L, Pruneri G, Carboni N, Capaccio P, Cesana B, Neri A . Clinical relevance of cyclin D1 protein overexpression in laryngeal squamous cell carcinoma. J Clin Oncol. 1998; 16(9):3069-77. DOI: 10.1200/JCO.1998.16.9.3069. View

20.

Namazie A, Alavi S, Olopade O, Pauletti G, Aghamohammadi N, Aghamohammadi M . Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors. Laryngoscope. 2002; 112(3):472-81. DOI: 10.1097/00005537-200203000-00013. View