title: Cell type-dependent biomarker expression in adenoid cystic carcinoma: biologic and therapeutic implications.
abstract: BACKGROUND
  Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by cellular, morphologic, and clinical heterogeneity. The authors of this report hypothesized that the dual cellular composition of ACC plays an important role in biomarker evaluation, tumor biologic behavior, and response to therapy.
  
  
  METHODS
  To investigate the differential localization and expression of the c-Kit protein and the epidermal growth factor receptor (EGFR) protein, immunohistochemical analyses were performed on tissue arrays that were constructed from 199 tumors, and the results were correlated with clinicopathologic factors.
  
  
  RESULTS
  c-Kit expression was limited to the inner ductal epithelial cells, whereas EGFR expression was limited mainly to the outer myoepithelial cells in the majority of ACCs with tubular and cribriform patterns. In solid ACCs, c-Kit uniformly was positive, whereas EGFR consistently was negative. A significant statistical correlation was observed between c-Kit expression and a poor 3-year outcome, and EGFR expression was correlated with a better 3-year outcome.
  
  
  CONCLUSIONS
  The current findings underscored the importance of cellular subtype localization of biomarkers in the clinical and therapeutic stratification of patients with ACC.
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Bell
authors.forename: Dianna
authors.initials: D
authors.lastname: Roberts
authors.forename: Merrill
authors.initials: M
authors.lastname: Kies
authors.forename: Pulivarthi
authors.initials: P
authors.lastname: Rao
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D003528:Carcinoma, Adenoid Cystic / Q000175:diagnosis*; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D012468:Salivary Gland Neoplasms / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit
references.citation: Mod Pathol. 2003 Dec;16(12):1224-31
references.pmid: 14681323
references.citation: J Oral Pathol Med. 2006 May;35(5):286-91
references.pmid: 16630292
references.citation: Mod Pathol. 2009 Oct;22(10):1296-302
references.pmid: 19617878
references.citation: J Clin Oncol. 2003 Jun 15;21(12):2237-46
references.pmid: 12748244
references.citation: Arch Otolaryngol Head Neck Surg. 1999 Feb;125(2):149-52
references.pmid: 10037280
references.citation: Cancer Lett. 2000 Jun 1;154(1):107-11
references.pmid: 10799746
references.citation: Head Neck. 2002 Jul;24(7):632-6
references.pmid: 12112535
references.citation: J Pathol. 1995 Nov;177(3):253-8
references.pmid: 8551387
references.citation: J Clin Oncol. 2004 Nov 15;22(22):4514-22
references.pmid: 15542802
references.citation: Gynecol Oncol. 2003 Oct;91(1):9-14
references.pmid: 14529657
references.citation: Histopathology. 2008 Nov;53(5):567-77
references.pmid: 18983466
references.citation: Clin Lung Cancer. 2004 Dec;6 Suppl 1:S20-3
references.pmid: 15638953
references.citation: Am J Clin Pathol. 2004 Jul;122(1):70-7
references.pmid: 15272532
references.citation: Science. 1998 Jan 23;279(5350):577-80
references.pmid: 9438854
references.citation: Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34
references.pmid: 15451219
references.citation: Oncologist. 2002;7 Suppl 4:31-9
references.pmid: 12202786
references.citation: Int J Cancer. 2001 Jun 20;96(3):149-58
references.pmid: 11410883
references.citation: JAMA. 2003 Oct 22;290(16):2149-58
references.pmid: 14570950
references.citation: J Mammary Gland Biol Neoplasia. 2005 Jul;10(3):249-60
references.pmid: 16807804
references.citation: Clin Cancer Res. 2008 Aug 15;14(16):5181-7
references.pmid: 18698036
references.citation: J Pathol. 2004 Mar;202(3):375-81
references.pmid: 14991904
references.citation: Am J Pathol. 2004 Jan;164(1):305-13
references.pmid: 14695343
references.citation: J Clin Oncol. 2002 Mar 15;20(6):1692-703
references.pmid: 11896121
references.citation: Laryngorhinootologie. 2002 Feb;81(2):98-105
references.pmid: 11914946
references.citation: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003 May;95(5):586-93
references.pmid: 12738950
references.citation: Cold Spring Harb Symp Quant Biol. 2005;70:343-56
references.pmid: 16869771
references.citation: Mod Pathol. 1998 Aug;11(8):728-34
references.pmid: 9720500
references.citation: Head Neck. 2004 Sep;26(9):829-31
references.pmid: 15350030
references.citation: J Mammary Gland Biol Neoplasia. 2000 Oct;5(4):379-91
references.pmid: 14973383
references.citation: Crit Rev Oncol Hematol. 1995 Jul;19(3):183-232
references.pmid: 7612182
references.citation: Mod Pathol. 2008 Sep;21(9):1168-75
references.pmid: 18587327
references.citation: Cancer Cell. 2008 May;13(5):394-406
references.pmid: 18455123
references.citation: N Engl J Med. 2003 Mar 13;348(11):994-1004
references.pmid: 12637609
references.citation: Mod Pathol. 1999 Oct;12(10):956-60
references.pmid: 10530560
references.citation: Clin Cancer Res. 2001 Oct;7(10):2958-70
references.pmid: 11595683
references.citation: J Clin Oncol. 2005 Jan 20;23(3):585-90
references.pmid: 15659505
references.citation: Int J Oral Maxillofac Surg. 2004 Jan;33(1):25-31
references.pmid: 14690656
references.citation: J Clin Oncol. 2003 Oct 15;21(20):3798-807
references.pmid: 12953099