Associations Between Mutations and Histologic Patterns of Mucin in Lung Adenocarcinoma

Kadota, Kyuichi; Yeh, Yi‐Chen; D’Angelo, Sandra P.; Moreira, André L.; Kuk, Deborah; Sima, Camelia S.; Riely, Gregory J.; Arcila, Maria E.; Kris, Mark G.; Rusch, Valerie W.; Adusumilli, Prasad S.; Travis, William D.

doi:10.1097/pas.0000000000000246

Cited by 137 publications

(62 citation statements)

References 43 publications

(70 reference statements)

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“…9–12 Moreover, EGFR and KRAS mutations that correlate with predominant histologic subtypes, according to this classification, have been identified. 11–14 However, correlations with other rare mutations (such as BRAF, PIK3CA, and NRAS ) and each predominant histologic subtype have not been thoroughly investigated and there is little data suggesting driver mutation status correlates with prognosis, within a single histologic subtype or within a specific tumor grade.…”

Section: Introductionmentioning

confidence: 99%

KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma

Kadota

Sima²,

Arcila³

et al. 2016

American Journal of Surgical Pathology

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Background The potential clinical impact of KRAS and epidermal growth factor receptor (EGFR) mutations has been investigated in lung adenocarcinomas; however, their prognostic value remains controversial. In our study, we sought to investigate the prognostic significance of driver mutations using a large cohort of early-stage lung adenocarcinomas. Methods We reviewed patients with pathologic early-stage, lymph node-negative, solitary lung adenocarcinoma who had undergone surgical resection (1995–2005; stage I/II = 463/19). Tumors were classified according to the IASLC/ATS/ERS classification and genotyped by Sequenom MassARRAY system and polymerase chain reaction-based assays. In stage I disease, the Kaplan-Meier method and cumulative incidence of recurrence (CIR) analyses were used to estimate the probability of overall survival (OS) and recurrence, respectively. Results Of all, 129 (27%) patients had mutations in KRAS, 86 (18%) in EGFR, 8 (2%) in BRAF, 8 (2%) in PIK3CA, 4 (1%) in NRAS, and 1 (0.2%) in AKT1. EGFR L858R mutation correlated with lepidic predominant histology (P = 0.006) while exon 19 deletion correlated with acinar predominant histology (P < 0.001). EGFR mutations were not detected in invasive mucinous adenocarcinomas (P = 0.033). The 5-year OS of patients with KRAS mutant tumors was significantly worse (n = 124; 5-year OS, 63%) than those with KRAS wild-type (n = 339; 77%; P < 0.001). In solid predominant tumors, KRAS mutations correlated with worse OS (P = 0.008) and increased risk of recurrence (P = 0.005). On multivariate analysis, KRAS mutation was an independent prognosticator of OS in all patients (hazard ratio, 1.87; P < 0.001) and recurrence in solid predominant tumors (hazard ratio, 4.73; P = 0.012). Conclusion In patients with resected stage I lung adenocarcinomas, KRAS mutation was an independent prognostic factor for OS and recurrence, especially in solid predominant tumors.

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Section: Introductionmentioning

confidence: 99%

KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma

Kadota

Sima²,

Arcila³

et al. 2016

American Journal of Surgical Pathology

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“…9, 10, 24-27 Some studies, especially those from the East Asian cohort, showed a positive association between EGFR mutations and the micropapillary subtype. 26, 28 The KRAS mutation showed a significant positive correlation with mucinous subtypes in some studies.…”

Section: Introductionmentioning

confidence: 99%

“…There were no reported differences among multiple ethnicities in ALK mutation positive population in 3 studies. 9, 23, 27 …”

Section: Introductionmentioning

confidence: 99%

The New IASLC-ATS-ERS Lung Adenocarcinoma Classification: What the Surgeon Should Know

Eguchi

Kadota

Park

et al. 2014

Seminars in Thoracic and Cardiovascular Surgery

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In 2011, a new histologic classification of lung adenocarcinomas was proposed from a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), based on the recommendation of an international and multidisciplinary panel. This classification proposed a method of comprehensive histologic subtyping (lepidic, acinar, papillary, micropapillary, and solid pattern) based on semi-quantitative assessment of histologic patterns (in 5% increments) with the ultimate goal of choosing a single, predominant pattern. Prognostic subsets could then be described for the classification. Patients with completely resected adenocarcinomas in situ (AIS) and minimally invasive adenocarcinomas (MIA) experienced low risk of recurrence. Patients with micropapillary or solid predominant tumors have a high risk for recurrence or cancer-related death. Patients with acinar and papillary predominant tumors comprise an intermediate-risk group. Herein, we review the outline of the proposed IASLC/ATS/ERS classification, a summary of published validation studies of this new classification and then discuss surgical key issues; we mainly focused on limited resection as an adequate treatment for early-stage lung adenocarcinomas as well as pre- and intraoperative diagnoses. We also review the published studies that identified the importance of histological subtypes in predicting recurrence, both rates and patterns, in early-stage lung adenocarcinomas. This new classification for the most common type of lung cancer is useful for surgeons, as its implementation would require only hematoxylin and eosin (H&E) histology slides, which is the common type of stain used in hospitals. It can be implemented with routine pathology evaluation and with no additional costs.

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“…EGFR exon 19 deletion, exon 21 L858R mutation, and KRAS exon 2 mutation were detected as previously described [20]. …”

Section: Methodsmentioning

confidence: 99%

“…The use of this well-annotated, previously reported cohort allowed us to assess the prognostic ability of all known clinical, surgical, pathological, histological, and molecular features indicative of aggressiveness—which included lymphatic and vascular invasion [4], type of surgical procedure [7, 19], histological subtypes (defined in the IASLC/ATS/ERS classification) [3, 7, 19], and EGFR and KRAS mutation status [20]. This expansive analysis, inclusive of all known high-risk factors, demonstrated that CCP score and mPS are independent prognostic markers for patients with stage I lung ADC.…”

Section: Introductionmentioning

confidence: 99%

Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

et al. 2016

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Purpose: The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes.Methods: Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer-specific mortality as the primary outcome.Results: In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer-specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14-2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer-specific mortality (HR=1.77; 95% CI, 1.18-2.66; P=0.006). Five-year lung cancer-specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer-specific survival (P<0.001 and 0.015, respectively), compared with low mPS.Conclusion: This study validates CCP score and mPS as independent prognostic markers for lung cancer-specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone.Oncotarget 35242 www.impactjournals.com/oncotarget

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Associations Between Mutations and Histologic Patterns of Mucin in Lung Adenocarcinoma

Cited by 137 publications

References 43 publications

KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma

KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma

The New IASLC-ATS-ERS Lung Adenocarcinoma Classification: What the Surgeon Should Know

Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

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