Clinicopathological Significance of Micropapillary Pattern in Lung Adenocarcinoma

et al. 2020

World J Surg Onc

Background: Several genetic driver alterations have been identified in micropapillary lung adenocarcinoma (MPA). However, the frequency of co-alteration of ROS1, EGFR, and EML4-ALK is yet unclear. Herein, we investigated the relationship between clinicopathologic characteristics and well-identified driver mutations of MPA compared with non-micropapillary lung adenocarcinoma (LA). Methods: Formalin-fixed paraffin-embedded (FFPE) sections derived from lung adenocarcinoma patients who never received adjuvant chemotherapy or radiation therapy prior to surgical resection were collected from October 2016 to June 2019. EGFR mutations, ROS1 rearrangements, and EML4-ALK fusion were identified in a set of 131 MPA and LA cases by using the amplification refractory mutation system (ARMS). The response rate and duration of response were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: EGFR mutations had occurred in 42 (76.4%) MPA patients and 42 (55.3%) LA patients. Interestingly, ROS1 rearrangements were highly enriched only in the MPA cases (6/55, 10.9%) but rarely in the LA cases (1/76, 1.3%). Furthermore, 7.3% (4/55) MPA samples had double gene mutations, while only 1.3% (1/76) LA cases had double gene alterations. Of 5 patients with harboring two driver oncogene mutations, four patients (80%) obtained partial response, and one patient (20%) suffered recurrence. Conclusions: A higher prevalence of ROS1 rearrangement or combined mutations of ROS1, EGFR, and EML4-ALK may play a critical role in the tumorigenesis of MPA. These findings provide a novel therapeutic strategy for patients with malignant MPA through combining TKIs than one TKI.

Section: Discussionsupporting

confidence: 93%

A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients

et al. 2020

World J Surg Onc

“…Consistent with previous reports [30,31], we here discovered that MPA has positive lymph node metastasis, positive pleural invasion, and earlier disease staging compared with LA (Table 1). Increasing studies have shown that a micropapillary component was associated with lymph node metastasis, pleural invasion and an early recurrence in stage I patients, suggesting MPA had a poorer prognosis compared with those without micropapillary component or other histological subtypes [32][33][34][35][36][37][38][39].…”

Section: Discussionsupporting

confidence: 93%

A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients

et al. 2020

Preprint

Background: Several genetic driver alterations have been identified in micropapillary lung adenocarcinoma (MPA). However, the frequency of co-alteration of ROS1, EGFR and EML4-ALK is yet unclear. Herein, we investigated the relationship between clinicopathologic characteristics and well-identified driver mutations of MPA compared with non-micropapillary lung adenocarcinoma (LA). Methods: Formalin fixed paraffin-embedded (FFPE) sections derived from lung adenocarcinoma patients who never received adjuvant chemotherapy or radiation therapy prior to surgical resection were collected from October 2016 to June 2019. EGFR mutations, ROS1 rearrangements and EML4-ALK fusion were identified in a set of 131 MPA and LA cases by using the Amplification Refractory Mutation System (ARMS). The response rate and duration of response were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: EGFR mutations had occurred in 42 (76.4%) MPA patients and 42 (55.3%) LA patients. Interestingly, ROS1 rearrangements were highly enriched only in the MPA cases (6/55, 10.9%) but rarely in the LA cases (1/76, 1.3%). Furthermore, 7.3% (4/55) MPA samples had double gene mutations, while only 1.3% (1/76) LA cases had double gene alterations. Of 5 patients with harboring two driver oncogenes mutations, four patients (80%) obtained partial response and one patient (20%) suffered recurrence. Conclusions: A higher prevalence of ROS1 rearrangement or combined mutations of ROS1, EGFR and EML4-ALK may play a critical role in the tumorigenesis of MPA. These findings provide a novel therapeutic strategy for patients with malignant MPA through combining TKIs than one TKI.

“…Like in previous reports [19,20], we here discovered that MPA has higher rate of lymph node metastasis and earlier disease stage compared with LA (Table 1). Increasing studies demonstrated that MPA had a poorer prognosis compared with those without micropapillary component or other histological subtypes [21][22][23][24][25][26][27].…”

Section: Discussionsupporting

confidence: 89%

A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients

et al. 2020

Preprint

Background: Several driver genetic alterations have been identified in micropapillary lung adenocarcinoma (MPA). However, the frequency of ROS1 rearrangements is yet unclear. Herein, we investigated the associations between clinicopathological and molecular characteristics of MPA compared with non-micropapillary lung adenocarcinoma (LA).Methods: FFPE sections derived from lung adenocarcinoma patients who never received adjuvant chemotherapy or radiation therapy prior to surgical resection were collected from October 2016 to June 2019. EGFR mutations, ROS1 rearrangements and EML4-ALK fusions were identified in a set of 131 MPA and LA cases by using the Amplification Refractory Mutation System.Results: EGFR mutations had occurred in 42 (76.4%) MPA patients and 42 (55.3%) LA patients. But interestingly, ROS1 rearrangement was present in 10.9% (6/55) MPA cases and 1.3% (1/76) LA cases. Moreover, 7.3% (4/55) MPA samples had multiple gene mutations, while only 1.3% (1/76) LA cases had double gene alterations.Conclusions: A higher prevalence of ROS1 rearrangements or combined mutations of ROS1 and EGFR or EML4-ALK may play a critical role in the tumorigenesis of MPA. These finding provides a novel therapy strategy for the patients with malignant MPA through combining TKIs than one TKI.