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http://dx.doi.org/10.7314/APJCP.2015.16.2.551

Roles of Immunohistochemical Staining in Diagnosing Pulmonary Squamous Cell Carcinoma  

Yan, Yue (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Zhang, Ya-Xiong (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Fang, Wen-Feng (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Kang, Shi-Yang (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Zhan, Jian-Hua (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Chen, Nan (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Hong, Shao-Dong (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Liang, Wen-Hua (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Tang, Yan-Na (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
He, Da-Cheng (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Wu, Xuan (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Zhang, Li (Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.2, 2015 , pp. 551-557 More about this Journal
Abstract
Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved. Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy. Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157). Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated.
Keywords
Non-small-cell lung cancer; pulmonary squamous cell carcinoma; epidermal growth factor receptor;
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1 Camilo R, Capelozzi VL, Siqueira SA, Del Carlo Bernardi F (2006). Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas. Hum Pathol, 37, 542-6.   DOI
2 Cataluna JJ, Perpina M, Greses JV, et al (1996). Cell type accuracy of bronchial biopsy specimens in primary lung cancer. Chest, 109, 1199-203.   DOI
3 Ciuleanu T, Brodowicz T, Zielinski C, et al (2009). Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet, 374, 1432-40.   DOI
4 Cohen MH, Gootenberg J, Keegan P, Pazdur R (2007). FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist, 12, 713-8.   DOI
5 Diez M, Cerdan FJ, Ortega MD, et al (1991). Evaluation of serum CA 125 as a tumor marker in non-small cell lung cancer. Cancer, 67, 150-4.   DOI
6 Diez M, Torres A, Pollan M, et al (1994). Prognostic significance of serum CA125 assay inpatients with NSCLC. Cancer, 73, 1368-76.   DOI
7 Ettinger DS, Akerley W, Bepler G, et al (2010). Non-small cell lung cancer. J Natl Compr Canc Netw, 8, 740-801.
8 Feinstein R, Gelfman NA, Yesner R (1970). Observer variability in the histopathologic diagnosis of lung cancer. Am Rev Respir Dis, 101, 671-84.
9 Ferlay J, Autier P, Boniol M, et al (2007). Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol, 18, 581-92.
10 Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.   DOI
11 Forbes SA, Bindal N, Bamford S, et al (2011). COSMIC: mining complete cancer genomes in the catalogue of somatic mutations in cancer. Nucleic Acids Res, 39, 945-50.   DOI
12 Ginsberg MS, Grewal RK, Heelan RT (2007). Lung cancer. Radiol Clin North Am, 45, 21-43.   DOI
13 Goldstraw P, Crowley J, Chansky K, et al (1993). The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours J Thorac Oncol 2007; 2: 706-714. Thorax, 48, 1135-9.   DOI
14 Grilley-Olson JE, Hayes DN, Moore DT, et al (2009). Diagnostic reproducibility of squamous cell carcinoma (SC) in the era of histology-directed non-small cell lung cancer (NSCLC) chemotherapy: a large prospective study. J Clin Oncol, 27, 15   DOI
15 Grilley-Olson JE, Hayes DN, Moore DT, et al (2013). Validation of interobserver agreement in lung cancer assessment: hematoxylin-eosin diagnostic reproducibility for non-small cell lung cancer: the 2004 World Health Organization classification and therapeutically relevant subsets. Arch Pathol Lab Med, 137, 32-40.   DOI
16 Guo P, Huang ZL, Yu P, Li K (2012). Trends in cancer mortality in China: an update. Ann Oncol, 23, 2755-62.   DOI   ScienceOn
17 Han JY, Park K, Kim SW, et al (2012). First-SIGNAL: first-line single-agent Iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol, 30, 1122-8.   DOI   ScienceOn
18 Hapani S, Sher A, Chu D, Wu S (2010). Increased risk of serious hemorrhage with bevacizumab in cancer patients: a metaanalysis. Oncology, 79, 27-38.   DOI   ScienceOn
19 Johansson L (2004). Histopathologic classification of lung cancer: Relevance of cytokeratin and TTF-1 immunophenotyping. Ann Diagn Pathol, 8, 259-67.   DOI   ScienceOn
20 Hata A, Katakami N, Yoshioka H, et al (2013). How sensitive are epidermal growth factor receptor-tyrosine kinase inhibitors for squamous cell carcinoma of the lung harboring EGFR gene-sensitive mutations? J Thorac Oncol, 8, 89-95.   DOI
21 Kargi D, Gurel B, Tuna (2007). Gurel, B. Appl Histochem Mol Morph, 15, 415-20.   DOI
22 Leighl NB (2012). Treatment paradigms for patients with metastatic non-small-cell lung cancer: first-, second-, and third-line. Curr Oncol, 19, S52-8.
23 Loo PS, Thomas SC, Nicolson MC, Fyfe MN, Kerr KM (2010). Subtyping of undifferentiated non-small cell carcinomas in bronchial biopsy specimens. J Thorac Oncol, 5, 442-7.   DOI
24 Maemondo M, Inoue A, Kobayashi K, et al (2010). Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med, 362, 2380-8.   DOI
25 Mitsudomi T, Morita S, Yatabe Y, et al (2010). Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol, 11, 121-8.   DOI
26 Mitsuhashi N, Takahashi T, Sakurai H, et al (1995). Establishment and characterization of a new human lung poorly differentiated adenocarcinoma cell line, GLL-11. Lung Cancer, 12, 13-24.   DOI
27 Mok TS, Wu YL, Thongprasert S, et al (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 361, 947-57.   DOI
28 Noh S, Shim H (2012). Optimal combination of immunohistochemical markers for subclassification of non-small cell lung carcinomas: A tissue microarray study of poorly differentiated areas. Lung Cancer, 76, 51-5.   DOI   ScienceOn
29 Nicholson AG, Gonzalez D, Shah P, et al (2010). Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis. J Thorac Oncol, 5, 436-41.   DOI
30 Nobre AR, Albergaria A, Schmitt F (2013). P40: A p63 isoform useful for lung cancer diagnosis -a review of the physiological and pathological role of p63. Acta Cytol, 57, 1-8.
31 Park SH, Ha SY, Lee JI, et al (2009). Epidermal growth factor receptor mutations and the clinical outcome in male smokers with squamous cell carcinoma of lung. J Korean Med Sci, 24, 448-52.   DOI
32 Paz-Ares L, de Marinis F, Dediu M, et al (2012). Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a doubleblind, phase 3, randomised controlled trial. Lancet Oncol, 13, 247-55.   DOI
33 Picardo AL, Diez M, Torres A, et al (1996). Analysis of the prognostic significance of cytosolic determination of CA125, CEA, SCC in patients with NSCLC. Cancer, 77, 1066-72.   DOI
34 Picardo AL, Torres AJ, Maestro M, et al (1994). Quantitative analysis of carcinoembryonic antigen, squamous cell carcinoma antigen, CA 125, and CA 50 cytosolic content in non-small cell lung cancer. Cancer, 73, 2305-11.   DOI
35 Rossi G, Pelosi G, Graziano P, Barbareschi M, Papotti M (2009). A reevaluation of the clinical significance of histological subtyping of non-small-cell lung carcinoma: diagnostic algorithms in the era of personalized treatments. Int J Surg Pathol, 17, 206-18.   DOI
36 Rekhtman N, Paik PK, Arcila ME, et al (2012). 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, 18, 1167-76.   DOI
37 Roggli VL, Vollmer RT, Greenberg SD, et al (1985). Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases. Hum Pathol, 16, 569-79.   DOI
38 Rosell R, Carcereny E, Gervais R, et al (2012). Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation -positive non-smallcell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol, 13, 239-46.   DOI   ScienceOn
39 Sandler A, Gray R, Perry MC, et al (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med, 355, 2542-50.   DOI
40 Scagliotti GV, Parikh P, von Pawel J, et al (2008). Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advancedstage non-small-cell lung cancer. J Clin Oncol, 26, 3543-51.   DOI
41 Shukuya T, Takahashi T, Kaira R, et al (2011). Efficacy of gefitinib for non-adenocarcinoma non-small-cell lung cancer patients harboring epidermal growth factor receptor mutations: a pooled analysis of published reports. Cancer Sci, 102, 1032-7.   DOI
42 Sigel CS, Moreira AL, Travis WD, et al (2011). Subtyping of non-small cell lung carcinoma: a comparison of small biopsy and cytology specimens. J Thorac Oncol, 6, 1849-56.   DOI
43 Thomas JS, Lamb D, Ashcroft T, et al (1993). How reliable is the diagnosis of lung cancer using small biopsy specimens? report of a UKCCCR lung cancer working party. Thorax, 48, 1135-9.   DOI
44 Sulpher JA, Owen SP, Hon H, et al (2013). Factors influencing a specific pathologic diagnosis of non-small-cell lung carcinoma. Clin Lung Cancer, 14, 238-44.   DOI
45 Syrigos KN, Vansteenkiste J, Parikh P, et al (2010). Prognostic and predictive factors in a randomized phase III trial comparing cisplatin-pemetrexed versus cisplatin-gemcitabine in advanced non-small-cell lung cancer. Ann Oncol, 21, 556-61.   DOI
46 Tanaka T, Matsuoka M, Sutani A, et al (2010). Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer, 126, 651-5.   DOI
47 Travis WD, Rekhtman N, Riley GJ, et al (2010). Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. J Thorac Oncol, 5, 411-4.   DOI
48 Wu YL, Zhong WZ, Li LY, et al (2007). Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a metaanalysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol, 2, 430-9.   DOI
49 Zhou C, Wu YL, Chen G, et al (2011). Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, openlabel, randomised, phase 3 study. Lancet Oncol, 12, 735-42.   DOI   ScienceOn
50 Alatas F, Alatas O, Metintas M, et al (2001). Diagnostic value of CEA, CA15-3, CA 19-9, CYFRA 21- 1, NSE and TSA assay in pleural effusions. Lung Cancer, 31, 9-16.   DOI
51 Beasley MB, Brambilla E, Travis WD (2005). The 2004 World Health Organization classification of lung tumors. Semin Roentgenol, 40, 90-7.   DOI
52 Bishop JA, Teruya-Feldstein J, Westra WH, et al (2012). P40 ($\Delta{Np63}$) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Modern Pathology, 25, 405-15.   DOI