Stromal myofibroblasts in potentially malignant and malignant lesions of the oral cavity

Rodrigues,Priscila   Campioni; Da Costa Miguel,Márcia  Cristina; De Aquino,Sibele   Nascimento; Fonseca,Felipe  Paiva; Dos Santos Silva,Alan  Roger; Paes Leme,Adriana  Franco; Coletta,Ricardo  D.

doi:10.3892/ol.2014.2763

Stromal myofibroblasts in potentially malignant and malignant lesions of the oral cavity

Authors:
- Priscila Campioni Rodrigues
- Márcia Cristina Da Costa Miguel
- Sibele Nascimento De Aquino
- Felipe Paiva Fonseca
- Alan Roger Dos Santos Silva
- Adriana Franco Paes Leme
- Ricardo D. Coletta
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Affiliations: Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, São Paulo 13414‑018, Brazil, Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, Campinas, São Paulo 13083‑970, Brazil
Published online on: December 3, 2014 https://doi.org/10.3892/ol.2014.2763
Pages: 667-670

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Abstract

Previous studies have demonstrated that myofibroblasts in the adjacent stroma are involved in the development and progression of malignant tumors. The aim of this study was to investigate the involvement of myofibroblasts in the progression of oral squamous cell carcinomas (OSCCs) by determining myofibroblast density in potentially malignant and malignant oral lesions. A total of 69 potentially malignant oral lesions (leukoplakias with mild, moderate or severe dysplasia), 90 OSCCs (well-, moderately and poorly differentiated), eight oral verrucous carcinomas and 29 fibrous hyperplasias were examined for the presence of myofibroblasts using immunohistochemical detection of isoform α of smooth muscle actin. Myofibroblasts were not identified in the adjacent stroma of fibrous hyperplasias and potentially malignant oral lesions, whereas 59.8% of the oral carcinomas exhibited myofibroblasts in various densities. The density was significantly higher in moderately and poorly differentiated OSCCs when compared with well‑differentiated tumors (P=0.04 and P=0.007, respectively). In verrucous carcinomas, the specific variant of well‑differentiated OSCC, stromal myofibroblasts were not detected. The results of the present study demonstrated that immunodetection of myofibroblasts does not aid with the determination of the malignant transformation potential of oral dysplasias, although moderately and poorly differentiated tumors exhibited a significantly higher density of myofibroblasts. The results reinforce the hypothesis that myofibroblasts may contribute to oral tumorigenesis, indicating that verification and monitoring of such may serve as a putative marker of OSCC behavior.

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1	Warnakulasuriya S: Living with oral cancer: Epidemiology with particular reference to prevalence and life-style changes that influence survival. Oral Oncol. 46:407–410. 2010. View Article : Google Scholar : PubMed/NCBI
2	Napier SS and Speight PM: Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med. 37:1–10. 2008. View Article : Google Scholar
3	Hsue SS, Wang WC, Chen CH, et al: Malignant transformation in 1458 patients with potentially malignant oral mucosal disorders: a follow-up study based in a Taiwanese hospital. J Oral Pathol Med. 36:25–29. 2007. View Article : Google Scholar
4	Hanahan D and Coussens LM: Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 21:309–322. 2012. View Article : Google Scholar : PubMed/NCBI
5	Alitalo A and Detmar M: Interaction of tumor cells and lymphatic vessels in cancer progression. Oncogene. 31:4499–4508. 2012. View Article : Google Scholar
6	De Wever O and Mareel M: Role of tissue stroma in cancer cell invasion. J Pathol. 200:429–447. 2003. View Article : Google Scholar : PubMed/NCBI
7	Desmouliere A, Guyot C and Gabbiani G: The stroma reaction myofibroblasts: a key player in the control of tumor cell behavior. Int J Dev Biol. 48:509–517. 2004. View Article : Google Scholar
8	De Wever O, Demetter P, Mareel M and Bracke M: Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer. 123:2229–2238. 2008. View Article : Google Scholar : PubMed/NCBI
9	Kellermann MG, Sobral LM, da Silva SD, et al: Myofibroblasts in the stroma of oral squamous cell carcinoma are associated with poor prognosis. Histopathology. 51:849–853. 2007. View Article : Google Scholar : PubMed/NCBI
10	Kellermann MG, Sobral LM, da Silva SD, et al: Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: Induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation. Oral Oncol. 44:509–517. 2008. View Article : Google Scholar
11	Bello IO, Vered M, Dayan D, et al: Cancer-associated fibroblasts, a parameter of the tumor microenvironment, overcomes carcinoma-associated parameters in the prognosis of patients with mobile tongue cancer. Oral Oncol. 47:33–38. 2011. View Article : Google Scholar
12	Marsh D, Suchak K, Moutasim KA, et al: Stromal features are predictive of disease mortality in oral cancer patients. J Pathol. 223:470–548. 2011. View Article : Google Scholar : PubMed/NCBI
13	Gale N, Pilch BZ, Sidransky D, El-Naggar AK, Westra W, Califano J, Johnson N and MacDonald DG: Epithelial precursor lesions (Oral cavity and oropharynx). World Health Organization Classification of Tumours. Pathology and Genetics of Head and Neck Tumours. Barnes L, Eveson JW, Reichart P and Sidransky D: IARC Press; Lyon: pp. 177–179. 2005
14	Baglole CJ, Ray DM, Bernstein SH, et al: More than structural cells, fibroblasts create and orchestrate the tumor microenvironment. Immunol Invest. 35:297–325. 2006. View Article : Google Scholar : PubMed/NCBI
15	Thode C, Jørgensen TG, Dabelsteen E, Mackenzie I and Dabelsteen S: Significance of myofibroblasts in oral squamous cell carcinoma. J Oral Pathol Med. 40:201–207. 2011. View Article : Google Scholar : PubMed/NCBI
16	Gabbiani G, Ryan GB and Majno G: Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 27:549–550. 1971. View Article : Google Scholar : PubMed/NCBI
17	Powell DW, Adegboyega PA, Di Mari JF and Mifflin RC: Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. Am J Physiol Gastrointest Liver Physiol. 289:G2–G7. 2005. View Article : Google Scholar : PubMed/NCBI
18	Barth PJ, Schenck ZU, Schweinsberg T, Ramaswamy A and Moll R: CD34+ fibrocytes, alpha-smooth muscle antigen positive myofibroblasts and CD117 expression in the stroma of invasive squamous cell carcinoma of the oral cavity, pharynx, and larynx. Virchows Arch. 444:231–234. 2004. View Article : Google Scholar : PubMed/NCBI
19	Kojc N, Zidar N, Vodopivec B and Gale N: Expression of CD34, alpha-smooth muscle actin, and transforming growth factor beta1 in squamous intraepithelial lesions and squamous cell carcinoma of the larynx and hypopharynx. Hum Pathol. 36:16–21. 2005. View Article : Google Scholar : PubMed/NCBI
20	Vered M, Allon I, Buchner A and Dayan D: Stromal myofibroblasts accompany modifications in the epithelial phenotype of tongue dysplastic and malignant lesions. Cancer Microenviron. 2:49–57. 2009. View Article : Google Scholar : PubMed/NCBI
21	Etemad-Moghadam S, Khalili M, Tirgary F and Alaeddini M: Evaluation of myofibroblasts in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol Med. 38:639–643. 2009. View Article : Google Scholar : PubMed/NCBI
22	Kawashiri S, Tanaka A, Noguchi N, et al: Significance of stromal desmoplasia and myofibroblast appearance at the invasive front in squamous cell carcinoma of the oral cavity. Head Neck. 31:1346–1353. 2009. View Article : Google Scholar : PubMed/NCBI
23	Vered M, Dobriyan A, Dayan D, et al: Tumor-host histopathologic variables, stromal myofibroblasts and risk score, are significantly associated with recurrent disease in tongue cancer. Cancer Sci. 101:274–280. 2010. View Article : Google Scholar
24	Seifi S, Shafaei S, Shafigh E, Sahabi SM and Ghasemi H: Myofibroblast stromal presence and distribution in squamous epithelial carcinomas, oral dysplasia and hyperkeratosis. Asian Pac J Cancer Prev. 11:359–364. 2010.PubMed/NCBI
25	Chaudhary M, Gadbail AR, Vidhale G, et al: Comparison of myofibroblasts expression in oral squamous cell carcinoma, verrucous carcinoma, high risk epithelial dysplasia, low risk epithelial dysplasia and normal oral mucosa. Head Neck Pathol. 6:305–313. 2012. View Article : Google Scholar : PubMed/NCBI
26	De-Assis EM, Pimenta LGGS, Costa-e-Silva E, Souza PEA and Horta MCR: Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal. 17:e733–e738. 2012. View Article : Google Scholar : PubMed/NCBI
27	Lewis MP, Lygoe KA, Nystrom ML, et al: Tumour-derived TGF-beta1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells. Br J Cancer. 90:822–832. 2004. View Article : Google Scholar : PubMed/NCBI
28	Sobral LM, Bufalino A, Lopes MA, et al: Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A. Oral Oncol. 47:840–846. 2011. View Article : Google Scholar : PubMed/NCBI
29	Hinsley EE, Kumar S, Hunter KD, Whawell SA and Lambert DW: Endothelin-1 stimulates oral fibroblasts to promote oral cancer invasion. Life Sci. 91:557–561. 2012. View Article : Google Scholar : PubMed/NCBI
30	Bremnes RM, Dønnem T, Al-Saad S, et al: The role of tumor stroma in cancer progression and prognosis: emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer. J Thorac Oncol. 6:209–217. 2011. View Article : Google Scholar
31	Alkan A, Bulut E, Gunhan O and Ozden B: Oral verrucous carcinoma: a study of 12 cases. Eur J Dent. 4:202–207. 2010.PubMed/NCBI