Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2012

Open Access 01-12-2012 | Research

Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study

Authors: Seok Ki Lee, Min Su Kwon, Yoon Se Lee, Seung-Ho Choi, Sang Yoon Kim, Kyoung Ja Cho, Soon Yuhl Nam

Published in: World Journal of Surgical Oncology | Issue 1/2012

Login to get access

Abstract

Background

Adenoid cystic cancer arising in the salivary glands has distinctive features such as perineural invasion, distant metastasis, and a variable prognosis. In salivary gland cancer, c-kit, EGFR, and VEGF are representative molecular markers that may predict remnant and recurrent tumors. In this study, the expression of c-kit, EGFR, and VEGF in adenoid cystic cancer was evaluated, and the relationships between the expression of these markers and the clinical findings were investigated.

Methods

The medical records of 48 patients who were treated for parotid adenoid cystic cancer from January 1990 to January 2006 were reviewed. The tumor location, size, histological subtypes, perineural invasion, the resected margin status, and lymph node metastasis were assessed. Immunohistochemical staining and semiquantitative analysis of c-kit, EGFR and VEGF were performed. The relationship between the expression of each marker and the clinicopathological factors were analyzed.

Results

Positive c-kit immunostaining was present in 45 patients (94%), with weak positivity (+1) in 23, moderate positivity (+2) in 19 and strong positivity (+3) in three. Positive EGFR immunostaining was observed in 27 (56%), with weak positivity (+1) in 19 and moderate positivity (+2) in eight with no strong positive staining. Positive VEGF immunostaining was present in 42 patients (88%) with weak positivity (+1) in 12, moderate positivity (+2) in 17, and strong positivity (+3) in 13. Only the expression of VEGF was significantly higher in parotid gland tumors than in any other gland (P = 0.032). Marginal involvement was associated with strong VEGF expression (P = 0.02). No marker was significantly correlated with recurrence or the survival rate. Lymph node status was related to the survival rate.

Conclusions

The expression of c-kit, EGRF, and VEGF had no predictive value for recurrence or the prognosis of adenoid cystic cancer. Only the lymph node status was related to the prognosis.
Appendix
Available only for authorised users
Literature
1.
Chen AM, Bucci MK, Weinberg V, Garcia J, Quivey JM, Schechter NR, Phillips TL, Fu KK, Eisele DW: Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys. 2006, 66: 152-159. 10.1016/j.ijrobp.2006.04.014.CrossRefPubMed
2.
Garden AS, Weber RS, Morrison WH, Ang KK, Peters LJ: The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. Int J Radiat Oncol Biol Phys. 1995, 32: 619-626. 10.1016/0360-3016(95)00122-F.CrossRefPubMed
3.
Mendenhall WM, Morris CG, Amdur RJ, Werning JW, Hinerman RW, Villaret DB: Radiotherapy alone or combined with surgery for adenoid cystic carcinoma of the head and neck. Head Neck. 2004, 26: 154-162. 10.1002/hed.10380.CrossRefPubMed
4.
Dodd RL, Slevin NJ: Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies. Oral Oncol. 2006, 42: 759-769. 10.1016/j.oraloncology.2006.01.001.CrossRefPubMed
5.
Elkin AD, Jacobs CD: Tamoxifen for salivary gland adenoid cystic carcinoma: report of two cases. J Cancer Res Clin Oncol. 2008, 134: 1151-1153. 10.1007/s00432-008-0377-3.CrossRefPubMed
6.
He JF, Ge MH, Zhu X, Chen C, Tan Z, Li YN, Gu ZY: Expression of RUNX3 in salivary adenoid cystic carcinoma: implications for tumor progression and prognosis. Cancer Sci. 2008, 99: 1334-1340. 10.1111/j.1349-7006.2008.00826.x.CrossRefPubMed
7.
Zhang J, Peng B, Chen X: Expressions of nuclear factor kappaB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome. Clin Cancer Res. 2005, 11: 7334-7343. 10.1158/1078-0432.CCR-05-0241.CrossRefPubMed
8.
DiPaola RS, Kuczynski WI, Onodera K, Ratajczak MZ, Hijiya N, Moore J, Gewirtz AM: Evidence for a functional kit receptor in melanoma, breast, and lung carcinoma cells. Cancer gene therapy. 1997, 4: 176-182.PubMed
9.
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998, 279: 577-580. 10.1126/science.279.5350.577.CrossRefPubMed
10.
Jeng YM, Lin CY, Hsu HC: Expression of the c-kit protein is associated with certain subtypes of salivary gland carcinoma. Cancer Lett. 2000, 154: 107-111. 10.1016/S0304-3835(00)00387-6.CrossRefPubMed
11.
Locati LD, Perrone F, Losa M, Mela M, Casieri P, Orsenigo M, Cortelazzi B, Negri T, Tamborini E, Quattrone P, Bossi P, Rinaldi G, Bergamini C, Calderone RG, Liberatoscioli C, Licitra L: Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs). Oral Oncol. 2009, 45: 986-990. 10.1016/j.oraloncology.2009.05.635.CrossRefPubMed
12.
Hotte SJ, Winquist EW, Lamont E, MacKenzie M, Vokes E, Chen EX, Brown S, Pond GR, Murgo A, Siu LL: Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study. J Clin Oncol. 2005, 23: 585-590.CrossRefPubMed
13.
Dassonville O, Formento JL, Francoual M, Ramaioli A, Santini J, Schneider M, Demard F, Milano G: Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer. J Clin Oncol. 1993, 11: 1873-1878.PubMed
14.
Gupta AK, McKenna WG, Weber CN, Feldman MD, Goldsmith JD, Mick R, Machtay M, Rosenthal DI, Bakanauskas VJ, Cerniglia GJ, Bernhard EJ, Weber RS, Muschel RJ: Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res. 2002, 8: 885-892.PubMed
15.
Xia W, Lau YK, Zhang HZ, Xiao FY, Johnston DA, Liu AR, Li L, Katz RL, Hung MC: Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res. 1999, 5: 4164-4174.PubMed
16.
Sorensen KB, Godballe C, de Stricker K, Krogdahl A: Parotid carcinoma: expression of kit protein and epidermal growth factor receptor. J Oral Pathol Med. 2006, 35: 286-291. 10.1111/j.1600-0714.2006.00421.x.CrossRefPubMed
17.
Dvorak HF, Brown LF, Detmar M, Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995, 146: 1029-1039.PubMedCentralPubMed
18.
Lim JJ, Kang S, Lee MR, Pai HK, Yoon HJ, Lee JI, Hong SP, Lim CY: Expression of vascular endothelial growth factor in salivary gland carcinomas and its relation to p53, Ki-67 and prognosis. J Oral Pathol Med. 2003, 32: 552-561.PubMed
19.
Younes MN, Park YW, Yazici YD, Gu M, Santillan AA, Nong X, Kim S, Jasser SA, El-Naggar AK, Myers JN: Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol Cancer Ther. 2006, 5: 2696-2705. 10.1158/1535-7163.MCT-05-0228.CrossRefPubMed
20.
Milano A, Longo F, Basile M, Iaffaioli RV, Caponigro F: Recent advances in the treatment of salivary gland cancers: emphasis on molecular targeted therapy. Oral Oncol. 2007, 43: 729-734. 10.1016/j.oraloncology.2006.12.012.CrossRefPubMed
21.
Ettl T, Schwarz S, Kleinsasser N, Hartmann A, Reichert TE, Driemel O: Overexpression of EGFR and absence of C-KIT expression correlate with poor prognosis in salivary gland carcinomas. Histopathology. 2008, 53: 567-577. 10.1111/j.1365-2559.2008.03159.x.CrossRefPubMed
22.
Beckhardt RN, Weber RS, Zane R, Garden AS, Wolf P, Carrillo R, Luna MA: Minor salivary gland tumors of the palate: clinical and pathologic correlates of outcome. Laryngoscope. 1995, 105: 1155-1160. 10.1288/00005537-199511000-00003.CrossRefPubMed
23.
Spiro RH: Management of malignant tumors of the salivary glands. Oncology (Williston Park). 1998, 12: 671-680. discussion 683
24.
Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC: Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008, 26: 626-632. 10.1200/JCO.2007.13.4452.CrossRefPubMed
25.
Alcedo JC, Fabrega JM, Arosemena JR, Urrutia A: Imatinib mesylate as treatment for adenoid cystic carcinoma of the salivary glands: report of two successfully treated cases. Head Neck. 2004, 26: 829-831. 10.1002/hed.20094.CrossRefPubMed
26.
Freier K, Flechtenmacher C, Walch A, Devens F, Muhling J, Lichter P, Joos S, Hofele C: Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland. Oral Oncol. 2005, 41: 934-939. 10.1016/j.oraloncology.2005.05.005.CrossRefPubMed
27.
Tsukitani K, Tatemoto Y, Noda Y, Mori M, Hayashi T, Kato K: Immunohistochemical detection of human epidermal growth factor in submandibular glands and their tumors using a polyclonal antiserum and a monoclonal antibody. Histochemistry. 1987, 87: 293-300. 10.1007/BF00492581.CrossRefPubMed
28.
Warburton G, Nikitakis NG, Roberson P, Marinos NJ, Wu T, Sauk JJ: Jr, Ord RA, Wahl SM: Histopathological and lymphangiogenic parameters in relation to lymph node metastasis in early stage oral squamous cell carcinoma. J Oral Maxillofac Surg. 2007, 65: 475-484. 10.1016/j.joms.2005.12.074.CrossRefPubMed
29.
Zhang H, Su SW, Zheng Y, Wang L, Ma XD: Expression of nuclear factor-kappa B mRNA, inducible nitric oxide synthase and interleukin-6 in nasal polyp and its role. Zhonghua Er Bi Yan Hou Ke Za Zhi. 2003, 38: 455-458.PubMed
30.
Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G: Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol. 2005, 23: 5474-5483. 10.1200/JCO.2005.04.192.CrossRefPubMed
31.
Kokemueller H, Eckardt A, Brachvogel P, Hausamen JE: Adenoid cystic carcinoma of the head and neck-a 20 years experience. Int J Oral Maxillofac Surg. 2004, 33: 25-31. 10.1054/ijom.2003.0448.CrossRefPubMed
32.
Agarwal JP, Jain S, Gupta T, Tiwari M, Laskar SG, Dinshaw KA, Chaturvedi P, D’Cruz AK, Shrivastava SK: Intraoral adenoid cystic carcinoma: prognostic factors and outcome. Oral Oncol. 2008, 44: 986-993. 10.1016/j.oraloncology.2008.01.004.CrossRefPubMed
33.
Rapidis AD, Givalos N, Gakiopoulou H, Faratzis G, Stavrianos SD, Vilos GA, Douzinas EE, Patsouris E: Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature. Oral Oncol. 2005, 41: 328-335. 10.1016/j.oraloncology.2004.12.004.CrossRefPubMed
34.
Le QT, Birdwell S, Terris DJ, Gabalski EC, Varghese A, Fee W, Goffinet DR: Postoperative irradiation of minor salivary gland malignancies of the head and neck. Radiother Oncol. 1999, 52: 165-171. 10.1016/S0167-8140(99)00084-5.CrossRefPubMed
35.
Spiro RH, Huvos AG: Stage means more than grade in adenoid cystic carcinoma. Am J Surg. 1992, 164: 623-628. 10.1016/S0002-9610(05)80721-4.CrossRefPubMed
36.
Li Q, Zhang XR, Liu XK, Liu ZM, Liu WW, Li H, Guo ZM: Long-term treatment outcome of minor salivary gland carcinoma of the hard palate. Oral Oncol. 2012, 48: 456-62. 10.1016/j.oraloncology.2011.12.005.CrossRefPubMed
37.
Spiro RH: Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg. 1997, 174: 495-498. 10.1016/S0002-9610(97)00153-0.CrossRefPubMed
38.
39.
Fisher B: Biological research in the evolution of cancer surgery: a personal perspective. Cancer Res. 2008, 68: 10007-10020. 10.1158/0008-5472.CAN-08-0186.CrossRefPubMed
40.
Weichselbaum RR, Hellman S: Oligometastases revisited. Nature Rev Clin Oncol. 2011, 8: 378-382.
41.
Ballonoff A, Raben D, Rusthoven KE, Bassetti M, Kane M, Song JI, Chen C: Outcomes of patients with n3 neck nodes treated with chemoradiation. Laryngoscope. 2008, 118: 995-998. 10.1097/MLG.0b013e31816a7120.CrossRefPubMed
Metadata
Title
Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study
Authors
Seok Ki Lee
Min Su Kwon
Yoon Se Lee
Seung-Ho Choi
Sang Yoon Kim
Kyoung Ja Cho
Soon Yuhl Nam
Publication date
01-12-2012
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2012
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-10-266

Other articles of this Issue 1/2012

World Journal of Surgical Oncology 1/2012 Go to the issue

Research

Skin-sparing mastectomy and immediate latissimus dorsi flap reconstruction: a retrospective analysis of the surgical and patient-reported outcomes

Technical innovations

A new feasible technique of mesh-reinforced pancreatojejunostomy and pancreatogastrostomy: retrospective analysis of 61 cases

Research

Clinical characteristics that distinguish eosinophilic organ infiltration from metastatic nodule development in cancer patients with eosinophilia

Research

Application of binding pancreatogastrostomy in laparoscopic central pancreatectomy

Case report

Leiomyosarcoma of the inferior vena cava level II involvement: curative resection and reconstruction of renal veins

Research

Is there any role of thrombin activatable fibrinolysis inhibitor in the development of a hypercoagulable state in gastric cancer