Chen-Tu Wu1, Mong-Wei Lin, Min-Shu Hsieh, Shuenn-Wen Kuo, Yih-Leong Chang. 1. Departments of *Pathology †Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ‡Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan.
Abstract
OBJECTIVE: For treatment decisions and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in metachronous multiple lung cancers to differentiate multiple primary lung cancers (MPLCs) from pulmonary metastases. BACKGROUND: The current criteria to differentiate MPLCs from metastases are based on the histologic type and onset interval and do not incorporate genetic analysis. The genetic background of MPLCs remains unclear. METHODS: Ninety-seven metachronous multiple lung cancers were identified to investigate somatic mutations in p53 and EGFR. Mutational analysis of p53 and EGFR was performed on DNA extracted from paraffin-embedded tumors. RESULTS: A high frequency of somatic mutations in p53 (44.3%; 43/97) and/or EGFR (51.5%; 50/97) resulted in a high discrimination rate of tumor clonality (77.3%; 75/97) in metachronous multiple lung cancers. Of the 97 cases, 25 cases (33.3%) and 50 cases (66.7%) were assessed as having the same clonality (SC) and different clonality (DC), respectively. Notably, DC was commonly observed among tumors of the same histologic type (60.7%; 37/61), which further supported the carcinogenic theory of field cancerization. Multivariate analysis revealed that a first primary tumor of 3 cm or smaller (5-year survival: 92.7%; P = 0.001) and a limited resection of the latest tumor (5-year survival: 96.0%; P = 0.016) were 2 independent predictors of favorable prognosis. CONCLUSIONS: Because most metachronous tumors of the same histologic type have different clonal origins, clonality assessment is essential to differentiate MPLCs from metastases. We recommend limited resection as the treatment of choice to achieve long-term survival in MPLCs patients with tumors of 3 cm or smaller.
OBJECTIVE: For treatment decisions and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in metachronous multiple lung cancers to differentiate multiple primary lung cancers (MPLCs) from pulmonary metastases. BACKGROUND: The current criteria to differentiate MPLCs from metastases are based on the histologic type and onset interval and do not incorporate genetic analysis. The genetic background of MPLCs remains unclear. METHODS: Ninety-seven metachronous multiple lung cancers were identified to investigate somatic mutations in p53 and EGFR. Mutational analysis of p53 and EGFR was performed on DNA extracted from paraffin-embedded tumors. RESULTS: A high frequency of somatic mutations in p53 (44.3%; 43/97) and/or EGFR (51.5%; 50/97) resulted in a high discrimination rate of tumor clonality (77.3%; 75/97) in metachronous multiple lung cancers. Of the 97 cases, 25 cases (33.3%) and 50 cases (66.7%) were assessed as having the same clonality (SC) and different clonality (DC), respectively. Notably, DC was commonly observed among tumors of the same histologic type (60.7%; 37/61), which further supported the carcinogenic theory of field cancerization. Multivariate analysis revealed that a first primary tumor of 3 cm or smaller (5-year survival: 92.7%; P = 0.001) and a limited resection of the latest tumor (5-year survival: 96.0%; P = 0.016) were 2 independent predictors of favorable prognosis. CONCLUSIONS: Because most metachronous tumors of the same histologic type have different clonal origins, clonality assessment is essential to differentiate MPLCs from metastases. We recommend limited resection as the treatment of choice to achieve long-term survival in MPLCs patients with tumors of 3 cm or smaller.
Authors: Julien P L Vincenten; Hendrik F van Essen; Birgit I Lissenberg-Witte; Nicole W J Bulkmans; Oscar Krijgsman; Daoud Sie; Paul P Eijk; Egbert F Smit; Bauke Ylstra; Erik Thunnissen Journal: PLoS One Date: 2019-10-16 Impact factor: 3.240