Absence of ALK and MET alterations in head and neck sarcomatoid carcinoma

Oral Oncology 58 (2016) e4–e5

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Letter to the editor Absence of ALK and MET alterations in head and neck sarcomatoid carcinoma

Sarcomatoid carcinoma (SC) of head and neck (HN) is a rare variant of the conventional squamous cell carcinoma that presents sarcomatoid features and poorer prognosis [1]. SC diagnosis is challenging because of overlapping morphological features with other spindle cell malignances and the rare prevalence of this disease. Treatment strategies are not different from other squamous cell carcinoma of HN district [2]. Recently, in a Asian woman with a relapsed refractory maxillary sinus SC harboring ALK translocation, a clinical benefit of crizotinib has been reported [3]. This clinical evidence could offer a new promising treatment choice for this relatively unresponsive entity considering also that in a small series of Asian population 20% of SC of HN showed ALK translocation [3]. The report prompted us to explore the molecular basis for a crizotinib treatment of SC of HN by performing a screening of the targets of this inhibitor including: rearrangements and expression of ALK, amplification, mutations and expression of MET and expression of ROS. Twenty-three Caucasian patients (19 male and 4 female; median age 65 years) with a confirmed diagnosis of primary SC of HN were retrospectively selected among patients treated for squamous cell cancer of head and neck from 2005 till 2011 at our Institute. The following subsites of disease were represented: larynx in 9, oropharynx in 5, oral cavity in 4, nasal cavity and ethmoid in 3, maxillary sinus in 2 patients. Treatment consisted in surgery alone in 5 cases, surgery followed by radiation in 12 cases and radiation or chemoradiation in 6 patients. ALK rearrangement was assessed by fluorescence in situ hybridization (FISH) using a break apart probe on FFPE tumoral sections. Unexpectedly, no ALK translocations were observed, whereas 4 of 23 (17%) cases showed a pattern consistent with gene amplification/ high polisomy of chromosome 2 and 14 (61%) cases showed low polysomy. However, in all but one cases, no ALK expression was observed by immunohistochemistry (IHC). These findings are in line with two previous studies reporting neither ALK rearrangements nor protein expression in pulmonary SC carrying ALK amplification (16.3–22%) [4,5]. As MET, the FISH assessment of MET gene status revealed no amplifications in our SC series even if two cases exhibited high polisomy coupled with MET null phenotype at IHC analysis. Furthermore, unlike to pulmonary SC, no MET and ALK coamplification was observed [5]. Since in pulmonary SC sensitivity to crizotinib was associated with MET exon 14 splice-site skipping mutations (which leads a smaller MET protein) [6], we interrogated for MET mutations the

http://dx.doi.org/10.1016/j.oraloncology.2016.05.015 1368-8375/Ó 2016 Elsevier Ltd. All rights reserved.

exon 14 and flanking introns by Sanger sequencing according to Liu et al. procedures [6]. No mutations were observed, at variance with pulmonary SC. Finally, Ros expression was investigated by IHC with negative results in all cases. In conclusion, despite the marginal occurrence of ALK gene amplification/high polisomy, we did not observed any ALK, MET and ROS deregulation in SC of HN. These results suggest that among Caucasian population the occurrence in HN SC of molecular alterations potentially targetable by crizotinib is a rare event, so discouraging a widespread analysis in this setting of disease. Conflict of interest statement None declared. References [1] Chang NJ, Kao D, Lee LY, et al. Sarcomatoid carcinoma in head and neck. Ann Plastic Surg 2013;71:S1–7. [2] Thompson LDR, Wieneke JA, Miettinen M, Heffner DK. Spindle cell (Sarcomatoid) carcinomas of the larynx. Am J Surg Pathol 2002;26(2):153–70. [3] Kim SM, Kim MJ, Jung HA, et al. Presence of anaplastic lymphoma kinase ALK translocation in sarcomatoid carcinoma of head and neck and treatment effect of crizotinib: a case series. Head Neck 2015;37(5):E66–9. [4] Pelosi G, Gasparini P, Cavazza A, et al. Multiparametric molecular characterization of pulmonary sarcomatoid carcinoma reveals a nonrandom amplification of anaplastic lymphoma kinase (ALK) gene. Lung Cancer 2012;77 (3):507–14. [5] Pelosi G, Gasparini P, Conte D, et al. Synergistic activation upon MET and ALK coamplification sustains targeted therapy in sarcomatoid carcinoma, a deadly subtype of lung cancer. J Thorac Oncol 2016;11(5):718–28. [6] Liu X, Jia Y, Stoopler MB, et al. Next-generation sequencing of pulmonary sarcomatoid carcinoma reveals high frequency of actonable MET gene mutations. J Clin Oncol 2015;34(8):794–802. 10.

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F. Perrone Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ⇑ Corresponding author at: Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Pathology, Laboratory of Experimental Molecular Pathology, G. Venezian 1, 20153 Milan Italy. Tel.: +39 0223902614; fax: +39 0223902877. E-mail address: [email protected] P. Bossi Head and Neck Cancer Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy B. Cortelazzi G.P. Dagrada N. Paielli Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Letter to the editor / Oral Oncology 58 (2016) e4–e5

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L. Licitra Head and Neck Cancer Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy S. Pilotti Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Available online 1 June 2016