Tsugumasa Kamata1,2,3, Akihiko Yoshida1, Kouya Shiraishi4, Koh Furuta5, Tomoo Kosuge3,6, Shun-ichi Watanabe2, Hisao Asamura7, Koji Tsuta1,8. 1. Division of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan. 2. Division of Thoracic Surgery, National Cancer Centre Hospital, Tokyo, Japan. 3. Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan. 4. Division of Genome Biology, National Cancer Centre Research Institute, Tokyo, Japan. 5. Division of Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan. 6. Division of Hepatobiliary and Pancreatic Surgery, National Cancer Centre Hospital, Tokyo, Japan. 7. Department of Surgery, Division of General Thoracic Surgery, School of Medicine, Keio University, Tokyo, Japan. 8. Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.
Abstract
AIMS: In lung adenocarcinoma (ADC), micropapillary carcinomas (MPCs) are associated with poor prognosis because these tumours exhibit higher metastatic potential. Despite this, there are no studies investigating the differences between mucinous and non-mucinous MPC. METHODS AND RESULTS: We evaluated the proportion of micropapillary components in lung ADCs, and compared the differences with respect to the presence or absence of associated mucin. Tumour specimens from 694 patients with consecutively resected primary lung ADC were reviewed, and 37 cases of invasive mucinous ADCs were excluded. A significant (≥5%) micropapillary component was noted in 320 (48.7%) of 657 evaluable cases. When the cases with micropapillary component were divided into 67 (20.9%) mucinous and 253 (79.1%) non-mucinous subtypes, tumours with mucinous micropapillary component exhibited significantly more aggressive pathological features, a higher proportion of HER2 mutations (P = 0.002) and ALK rearrangements (P < 0.001), and a lower proportion of EGFR mutations (P = 0.038) compared to those with a non-mucinous micropapillary component. In survival analyses, mucinous MPC tended to be more aggressive compared with non-mucinous MPC, but its prognostic value was not statistically significant (P = 0.076). CONCLUSIONS: Mucinous micropapillary pattern is an under-recognized unique growth associated significantly with HER2 mutation and ALK rearrangement.
AIMS: In lung adenocarcinoma (ADC), micropapillary carcinomas (MPCs) are associated with poor prognosis because these tumours exhibit higher metastatic potential. Despite this, there are no studies investigating the differences between mucinous and non-mucinous MPC. METHODS AND RESULTS: We evaluated the proportion of micropapillary components in lung ADCs, and compared the differences with respect to the presence or absence of associated mucin. Tumour specimens from 694 patients with consecutively resected primary lung ADC were reviewed, and 37 cases of invasive mucinous ADCs were excluded. A significant (≥5%) micropapillary component was noted in 320 (48.7%) of 657 evaluable cases. When the cases with micropapillary component were divided into 67 (20.9%) mucinous and 253 (79.1%) non-mucinous subtypes, tumours with mucinous micropapillary component exhibited significantly more aggressive pathological features, a higher proportion of HER2 mutations (P = 0.002) and ALK rearrangements (P < 0.001), and a lower proportion of EGFR mutations (P = 0.038) compared to those with a non-mucinous micropapillary component. In survival analyses, mucinous MPC tended to be more aggressive compared with non-mucinous MPC, but its prognostic value was not statistically significant (P = 0.076). CONCLUSIONS: Mucinous micropapillary pattern is an under-recognized unique growth associated significantly with HER2 mutation and ALK rearrangement.
Authors: Johanna S M Mattsson; Hans Brunnström; Verena Jabs; Karolina Edlund; Karin Jirström; Stephanie Mindus; Linnéa la Fleur; Fredrik Pontén; Mats G Karlsson; Christina Karlsson; Hirsh Koyi; Eva Brandén; Johan Botling; Gisela Helenius; Patrick Micke; Maria A Svensson Journal: BMC Cancer Date: 2016-08-05 Impact factor: 4.430