Patología y Estudios Moleculares en el Cáncer de Pulmón de Células no Pequeñas (CPCNP): 2do consenso nacional de la sociedad panameña de oncología (SPO). (Mesa 3)

Alejandro Crismatt, I Barrera, K Gonzalez, A Crismatt

Resumen


Resumen
En la última década el diagnóstico histopatológico se ha vuelto un determinante importante para el tratamiento del cáncer de pulmón de células no pequeñas (CPCNP). Un número creciente de pacientes se benefician de terapias blancos dirigidas a alteraciones moleculares particulares (Mutaciones, genes de Fusión...etc.), por lo tanto, el diagnóstico preciso y las pruebas de laboratorio basadas en biomarcadores predictivos para la determinación de los pacientes que más probablemente respondan a las terapias blanco, representan un cambio en el paradigma diagnóstico del cáncer de pulmón y son ahora un estándar[1]. El diagnóstico histopatológico del cáncer de pulmón es un proceso de múltiples pasos que inicia con el diagnóstico morfológico para determinar el tipo histológico (refinado por la inmuno-histoquímica en los casos requeridos), seguido de la caracterización molecular del tumor.  La creciente complejidad del algoritmo diagnóstico representa nuevos retos para los pacientes con cáncer de pulmón, dentro de los cuales destaca la disponibilidad de suficiente tejido para realización de todas las pruebas moleculares. La mayoría de los CPCNP son diagnosticados en etapas avanzadas de la enfermedad, por lo que las grandes muestras de tumor (resección quirúrgica) se obtienen solo en unos pocos casos. Por lo tanto, es imperativo que toda adquisición de tejido tumoral se maximice para lograr realizar las pruebas moleculares requeridas. El rol del equipo multidisciplinario que incluye al neumólogo, radiólogo, patólogo, cirujano torácico y oncólogo es esencial para determinar el mejor abordaje de cada paciente[2,3].

[Pathology and Molecular Studies in Non Small Cell Lung Cancer (CPCNP): 2nd national consensus of the Panamanian Oncology Society (SPO).]

Abstract
In the last decade, histopathological diagnosis has become an important determinant for the treatment of non-small cell lung cancer (NSCLC). A growing number of patients benefit from therapies targeting particular molecular alterations (Mutations, Fusion genes... etc.), thus accurate diagnosis and laboratory tests based on predictive biomarkers for the determination of patients who more likely to respond to target therapies, represent a change in the diagnostic paradigm of lung cancer and are now a standard[1]. The histopathological diagnosis of lung cancer is a multi-step process that begins with the morphological diagnosis to determine the histological type (refined by immunohistochemistry in the required cases), followed by the molecular characterization of the tumor. The increasing complexity of the diagnostic algorithm represents new challenges for patients with lung cancer, in which the availability of sufficient tissue for the realization of all molecular tests stands out. Most NSCLC are diagnosed in advanced stages of the disease, so large tumor samples (surgical resection) are obtained only in a few cases. Therefore, it is imperative that any acquisition of tumor tissue is maximized to achieve the required molecular tests. The role of the multidisciplinary team that includes the pulmonologist, radiologist, pathologist, thoracic surgeon and oncologist is essential to determine the best approach for each patient[2,3].


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Referencias


Kerr KM, Bubendorf L, Novello S et al. Second ESMO consensus conference on lung cancer: Pathology and molecular biomarkers for non-small-cell lung cancer. Annals of Oncology. 2014;25[9]:1681-1690

Kerr KM. Personalized medicine for lung cancer: new challenges for pathology. Histopathology 2012; 60: 531–546.

Thunnissen E, Kerr KM, Herth FJ et al. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group. Lung Cancer 2012; 76: 1–18.

Lim E, Baldwin D, Beckles M et al. Guidelines on the radical management of patients with lung cancer. Thorax 2010; 65(suppl III): iii1–iii27.

Felip E, Gridelli C, Baas P et al. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010. Ann Oncol 2011; 22: 1507–1519.

Neumeister VM, Anagnostou V, Siddiqui S et al. Quantitative assessment of effect of preanalytic cold ischemic time on protein expression in breast cancer tissues. J Natl Cancer Inst 2012; 104: 1815–1824.

Portier BP, Wang Z, Downs-Kelly E et al. Delay to formalin fixation ‘cold ischemia time’: effect on ERBB2 detection by in-situ hybridization and immunohistochemistry. Mod Pathol 2013; 26: 1–9.

Engel KB, Moore HM. Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin-embedded tissue. Arch Pathol Lab Med 2011; 135: 537–543.

Arber DA. Effect of prolonged formalin fixation on the immunohistochemical reactivity of breast markers. Appl Immunohistochem Mol Morphol 2002; 10: 183–186.

Babic A, Loftin IR, Stanislaw S et al. The impact of pre-analytical processing on staining quality for H&E, dual hapten, dual color in situ hybridization and fluorescent in situ hybridization assays. Methods 2010; 52: 287–300.

Chafin D, Theiss A, Roberts E et al. Rapid two-temperature formalin fixation. PloS One 2013; 8: e54138.

Lindeman NI, Cagle PT, Beasley MB et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase Inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol 2013; 8: 823–859.

Travis W, Brambilla E, Nicholson A, et al. The 2015 World Health Organization Classification of Lung Tumors Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification: J Thorac Oncology. 2015 Sep[10] 9: 1243-1260.

Thomas JS, Lamb D, Ashcroft T et al. How reliable is the diagnosis of lung cáncer using small biopsy specimens? Report of a UKCCCR Lung Cancer Working Party. Thorax 1993; 48: 1135–1139.

Edwards SL, Roberts C, McKean ME et al. Preoperative histological classification of primary lung cancer: accuracy of diagnosis and use of the non-small cell category. J Clin Pathol 2000; 53: 537–540.

Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer: summary of published evidence. Chest 2003; 123; 115S–128S.

Rivera MP, Detterbeck F, Mehta AC, American College of Chest Physicians. Diagnosis of lung cancer: the guidelines. Chest 2003; 123: 129S–136S.

Burnett RA, Howatson SR, Lang S et al. Observer variability in histopathological reporting of non-small cell carcinoma on bronchial biopsy specimens. J Clin Pathol 1996; 49: 130–133.

Cataluña JJ, Perpiñá M, Greses JV et al. Cell type accuracy of bronchial biopsy specimens in primary lung cancer. Chest 1996; 109: 1199–1203.

Matsuda M, Horai T, Nakamura S et al. Bronchial brushing and bronchial biopsy: comparison of diagnostic accuracy and cell typing reliability in lung cancer. Thorax 1986; 41: 475–478.

Chuang MT, Marchevsky A, Teirstein AS et al. Diagnosis of lung cancer by fibreoptic bronchoscopy: problems in the histological classification of non-small cell carcinomas. Thorax 1984; 39: 175–178.

Loo PS, Thomas SC, Nicolson MC et al. Subtyping of undifferentiated non-small cell carcinomas in bronchial biopsy specimens. J Thorac Oncol 2010; 5:442–447.

Mukhopadhyay S, Katzenstein AL. Subclassification of non-small cell lacking morphologic differentiation on biopsy specimens: utility of an immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6. Am J Surg Pathol 2011; 35: 15–25.

Terry J, Leung S, Laskin J et al. Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples. Am J Surg Pathol 2010; 34: 1805–1811.

Righi L, Graziano P, Fornari A et al. Immunohistochemical subtyping of non-small cell lung cancer not otherwise specified in fine-needle aspiration cytology: a retrospective study of 103 cases with surgical correlation. Cancer 2011; 117: 3416–3423.

Bishop JA, Teruya-Feldstein J, Westra WH et al. p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol 2012; 25: 405–415.

Wallace WA, Rassl DM. Accuracy of cell typing in non-small cell lung cancer by EBUS/EUS-FNA cytological samples. Eur Respir J 2011; 38: 911–917.

Travis WD, Brambilla E, Noguchi M et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6: 244–285.

Travis WD, Brambilla E, Noguchi M et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification. Arch Pathol Lab Med 2013; 137: 668–684.

Sartori G, Cavazza A, Sgambato A et al. EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am J Clin Pathol 2009; 131: 478–489.

Marchetti A, Martella C, Felicioni L et al. EGFR mutations in non-small cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol 2005; 23: 857–865.

Tsao AS, Tang XM, Sabloff B et al. Clinicopathologic characteristics of the EGFR gene mutation in non-small cell lung cancer. J Thorac Oncol 2006; 1: 231–239.

Pham DK, Kris MG, Riely GJ et al. Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas. J Clin Oncol 2006; 24: 1700–1704.

Rosell R, Carcereny E, Gervais R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012; 13: 239–246.

Zhou C, Wu YL, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non small-cell lung cáncer (OPTIMAL, CTONG-0802): a multicentre, open-label randomized phase 3 study. Lancet Oncol 2011; 12: 735–742.

Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957.

Mitsudomi T, Morita S, Yatabe Y et al. 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, randomized phase 3 trial. Lancet Oncol 2010; 11: 121–128.

Sequist LV, Yang JC, Yamamoto N et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013; 31: 3327–3334.

Li AR, Chitale D, Riely GJ et al. EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression. J Mol Diagn 2008; 10: 242–248.

Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7: 169–181.

Sequist LV, Waltman BA, Dias-Santagata D et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011; 3: 75ra26.

Soda M, Choi YL, Enomoto M et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448: 561–566.

Shaw AT, Yeap BY, Mino-Kenudson M et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009; 27: 4247–4253.

Inamura K, Takeuchi K, Togashi Y et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol 2008; 3: 13–17.

Takahashi T, Sonobe M, Kobayashi M et al. Clinicopathologic features of nonsmall- cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol 2010; 17[3]: 889–897.

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: 768–769.

Wong DW, Leung EL, So KK et al. University of Hong Kong Lung Cancer Study Group. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 2009; 115: 1723–1733.

Zhang X, Zhang S, Yang X et al. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. Mol Cancer 2010; 9: 188.

Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. New England Journal of Medicine. 2014 Dec 4; 371[23]:2167-77.

Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC. Crizotinib in ROS1-rearranged non–small-cell lung cancer. New England Journal of Medicine. 2014 Nov 20; 371[21]:1963-71.

Planchard D, Besse B, Rigas JR, et al. Dabrafenib plus trametinib in patients with previously treated BRAF V600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. The Lancet Oncology. 2016 Jul 31; 17[7]:984-93.

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. New England Journal of Medicine. 2016 Nov 10; 375[19]:1823-33.

Aisner D, Rumery M, Merrick D et al. Do more with less, Tips and techniques for maximizing small biopsy and cytology specimens for molecular and ancillary testing: The University of Colorado Experience. Arch Pathol Lab Med. Vol 140. Nov 2016; 1206-1220.

Dietel M, Bubendorf L, Dingemans AM, et al. Diagnostic procedures for non-small-cell lung cáncer (NSCLC): Recommendations of the European Expert Group; Thorax 2016; 71:177–184.


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