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Can we eliminate squamous cell carcinoma of the lung from testing of EML4-ALK fusion gene?
Lung Cancer 79 (2013) 94–96
Contents lists available at SciVerse ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Letters to the Editor Can we eliminate squamous cell carcinoma of the lung from testing of EML4-ALK fusion gene? To the Editors, We read with great interest the recent article written by Just et al. [1], entitled “Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALKrearrangement in lung cancer: a comprehensive study of Caucasian non-smokers”. They proposed a diagnostic algorithm for the identification of ALK rearrangement in lung cancer. At first screening, adenocarcinoma without mutation of EGFR or KRAS should be examined using anti-ALK immunohistochemistry. Since the estimated prevalence of EML4-ALK in squamous cell carcinoma of the lung is only ∼1% [2], its testing in the histology is not routinely recommended in the National Comprehensive Cancer Network guideline for the treatment of NSCLC (version 3, 2012), either. A 45-year-old Japanese woman with 25 pack-year history of smoking visited our hospital because of left back and abdominal pain. Chest X-ray and computed tomography revealed a mass in the left hilar area with pleural invasion. She was diagnosed
as squamous cell carcinoma of the lung with wild type-EGFR by bronchoscopy. Although her tumor was moderately differentiated squamous cell carcinoma (Fig. 1A and B), immunohistochemistry using the iAEP method (ALK Detection Kit; Nichirei Bioscience, Tokyo, Japan) showed positive ALK expression (Fig. 1C). Subsequently, an EML4-ALK gene rearrangement was confirmed by fluorescence in situ hybridization (Fig. 1D). To determine histological subtype furthermore, we performed immunostaining for thyroid transcription factor-1, p40 and p63 (Fig. 2A–D). These results were consistent with the histopathological diagnosis of squamous cell carcinoma in this specimen. Crizotinib is the first orally available ALK inhibitor and is proved to be effective for EML4-ALK fusion gene-positive NSCLC [3]. We understand that the patients with squamous cell carcinoma have rarely EML4-ALK fusion gene. However, if they had it, they might be eliminated from the opportunity to receive the effective drug. Histopathological diagnosis is often made on the basis of a small fraction of the tumor tissue yielded by bronchoscopy. The specimen could not always represent the precise characteristics of the whole tumor [4]. Moreover, Chaft et al. recently described adenosquamous lung cancer masquerading as pure squamous cell carcinoma
Fig. 1. Histopathological and immunohistological findings. (A and B) Hematoxylin and eosin staining showed moderately differentiated squamous cell carcinoma (A: 40×; B: 100×, inset: 400×). (C) ALK protein was overexpressed with immunohistochemistry (40×, inset: 400×). (D) The tumor was positive for EML4-ALK rearrangement using a break-apart fluorescent in situ hybridization probe (60% of cells harboring isolated 3 ALK FISH signals).
0169-5002/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
Letters to the Editor / Lung Cancer 79 (2013) 94–96
95
Fig. 2. Immunostaining for thyroid transcription factor-1, p40 and p63 The tumor was negative for thyroid transcription factor-1 (A: 100×), positive for p40 (B: 100×), and partially positive for p63 (C: 100×, D: 400×).
with ALK rearrangement [5]. In our case, ALK positive squamous cell carcinomas in a biopsy might be the squamous component of an adenosquamous carcinoma. In addition, An et al. recently reported that EML4-ALK fusion gene was detected in four of 62 patients (6.5%) in the smokers with squamous cell carcinoma [6] such as our case. Oncologist should be aware of the existence of patients harboring EML4-ALK positive-squamous cell carcinoma of the lung.
Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, Japan Yasumasa Monobe Department of Pathology 1, Kawasaki Hospital, Kawasaki Medical School, Japan ∗ Corresponding
author at: Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, 2-1-80, Nakasange, Kita-ku, Okayama 700-8505, Japan. Tel.: +81 86 225 2111; fax: +81 86 232 8343. E-mail addresses: [email protected], [email protected] (N. Takigawa)
Conflict of interest statement None declared. References
7 August 2012
[1] Just PA, Cazes A, Audebourg A, Cessot A, Pallier K, Danel C, et al. Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALK-rearrangement in lung cancer: a comprehensive study of Caucasian non-smokers. Lung Cancer 2012;76:309–15. [2] Perez-Moreno P, Brambilla E, Thomas R, Soria JC. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res 2012;18:2443–51. [3] Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363:1693–703. [4] Rekhtman N, Paik PK, Arcila ME, Tafe LJ, Oxnard GR, Moreira AL, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res 2012;18:1167–76. [5] Chaft JE, Rekhtman N, Ladanyi M, Riely GJ. ALK-rearranged lung cancer: adenosquamous lung cancer masquerading as pure squamous carcinoma. J Thorac Oncol 2012;7:768–9. [6] An SJ, Chen ZH, Su J, Zhang XC, Zhong WZ, Yang JJ, et al. Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status. PLoS ONE 2012;7:e40109.
Nobuaki Ochi Hiromichi Yamane Tomoko Yamagishi Nagio Takigawa ∗
doi:10.1016/j.lungcan.2012.09.017
Human papillomaviruses (HPVs) in lung cancer: A causative trigger or just a co-incidence? Keywords: Human papillomaviruses HPV Lung cancer
Editor, We read with interest the study by Kato et al. [1], which detected HPV DNA in 17% of the examined 42 lung tumors, suggesting that HPV presence in lung cancer may be significantly related to EGFR mutations. Lung cancer is a worldwide leading cause of mortality strongly associated with the smoking habit since 1900s [2]. However, during the last decade literature reporting the presence of HPVs in lung cancer has expanded rapidly, supporting a viral etiology for a subset
Contents lists available at SciVerse ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Letters to the Editor Can we eliminate squamous cell carcinoma of the lung from testing of EML4-ALK fusion gene? To the Editors, We read with great interest the recent article written by Just et al. [1], entitled “Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALKrearrangement in lung cancer: a comprehensive study of Caucasian non-smokers”. They proposed a diagnostic algorithm for the identification of ALK rearrangement in lung cancer. At first screening, adenocarcinoma without mutation of EGFR or KRAS should be examined using anti-ALK immunohistochemistry. Since the estimated prevalence of EML4-ALK in squamous cell carcinoma of the lung is only ∼1% [2], its testing in the histology is not routinely recommended in the National Comprehensive Cancer Network guideline for the treatment of NSCLC (version 3, 2012), either. A 45-year-old Japanese woman with 25 pack-year history of smoking visited our hospital because of left back and abdominal pain. Chest X-ray and computed tomography revealed a mass in the left hilar area with pleural invasion. She was diagnosed
as squamous cell carcinoma of the lung with wild type-EGFR by bronchoscopy. Although her tumor was moderately differentiated squamous cell carcinoma (Fig. 1A and B), immunohistochemistry using the iAEP method (ALK Detection Kit; Nichirei Bioscience, Tokyo, Japan) showed positive ALK expression (Fig. 1C). Subsequently, an EML4-ALK gene rearrangement was confirmed by fluorescence in situ hybridization (Fig. 1D). To determine histological subtype furthermore, we performed immunostaining for thyroid transcription factor-1, p40 and p63 (Fig. 2A–D). These results were consistent with the histopathological diagnosis of squamous cell carcinoma in this specimen. Crizotinib is the first orally available ALK inhibitor and is proved to be effective for EML4-ALK fusion gene-positive NSCLC [3]. We understand that the patients with squamous cell carcinoma have rarely EML4-ALK fusion gene. However, if they had it, they might be eliminated from the opportunity to receive the effective drug. Histopathological diagnosis is often made on the basis of a small fraction of the tumor tissue yielded by bronchoscopy. The specimen could not always represent the precise characteristics of the whole tumor [4]. Moreover, Chaft et al. recently described adenosquamous lung cancer masquerading as pure squamous cell carcinoma
Fig. 1. Histopathological and immunohistological findings. (A and B) Hematoxylin and eosin staining showed moderately differentiated squamous cell carcinoma (A: 40×; B: 100×, inset: 400×). (C) ALK protein was overexpressed with immunohistochemistry (40×, inset: 400×). (D) The tumor was positive for EML4-ALK rearrangement using a break-apart fluorescent in situ hybridization probe (60% of cells harboring isolated 3 ALK FISH signals).
0169-5002/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
Letters to the Editor / Lung Cancer 79 (2013) 94–96
95
Fig. 2. Immunostaining for thyroid transcription factor-1, p40 and p63 The tumor was negative for thyroid transcription factor-1 (A: 100×), positive for p40 (B: 100×), and partially positive for p63 (C: 100×, D: 400×).
with ALK rearrangement [5]. In our case, ALK positive squamous cell carcinomas in a biopsy might be the squamous component of an adenosquamous carcinoma. In addition, An et al. recently reported that EML4-ALK fusion gene was detected in four of 62 patients (6.5%) in the smokers with squamous cell carcinoma [6] such as our case. Oncologist should be aware of the existence of patients harboring EML4-ALK positive-squamous cell carcinoma of the lung.
Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, Japan Yasumasa Monobe Department of Pathology 1, Kawasaki Hospital, Kawasaki Medical School, Japan ∗ Corresponding
author at: Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, 2-1-80, Nakasange, Kita-ku, Okayama 700-8505, Japan. Tel.: +81 86 225 2111; fax: +81 86 232 8343. E-mail addresses: [email protected], [email protected] (N. Takigawa)
Conflict of interest statement None declared. References
7 August 2012
[1] Just PA, Cazes A, Audebourg A, Cessot A, Pallier K, Danel C, et al. Histologic subtypes, immunohistochemistry, FISH or molecular screening for the accurate diagnosis of ALK-rearrangement in lung cancer: a comprehensive study of Caucasian non-smokers. Lung Cancer 2012;76:309–15. [2] Perez-Moreno P, Brambilla E, Thomas R, Soria JC. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin Cancer Res 2012;18:2443–51. [3] Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363:1693–703. [4] Rekhtman N, Paik PK, Arcila ME, Tafe LJ, Oxnard GR, Moreira AL, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res 2012;18:1167–76. [5] Chaft JE, Rekhtman N, Ladanyi M, Riely GJ. ALK-rearranged lung cancer: adenosquamous lung cancer masquerading as pure squamous carcinoma. J Thorac Oncol 2012;7:768–9. [6] An SJ, Chen ZH, Su J, Zhang XC, Zhong WZ, Yang JJ, et al. Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status. PLoS ONE 2012;7:e40109.
Nobuaki Ochi Hiromichi Yamane Tomoko Yamagishi Nagio Takigawa ∗
doi:10.1016/j.lungcan.2012.09.017
Human papillomaviruses (HPVs) in lung cancer: A causative trigger or just a co-incidence? Keywords: Human papillomaviruses HPV Lung cancer
Editor, We read with interest the study by Kato et al. [1], which detected HPV DNA in 17% of the examined 42 lung tumors, suggesting that HPV presence in lung cancer may be significantly related to EGFR mutations. Lung cancer is a worldwide leading cause of mortality strongly associated with the smoking habit since 1900s [2]. However, during the last decade literature reporting the presence of HPVs in lung cancer has expanded rapidly, supporting a viral etiology for a subset