Michaël Duruisseaux1, Martine Antoine2, Nathalie Rabbe1, Anita Rodenas3, Anne Mc Leer-Florin4, Roger Lacave5, Virginie Poulot6, Belinda Duchêne7, Isabelle Van Seuningen7, Jacques Cadranel8, Marie Wislez9. 1. Sorbonne Universités, UPMC Univ. Paris 06, GRC no 04, Theranoscan, 4 rue de la Chine, F-75252 Paris, France. 2. Sorbonne Universités, UPMC Univ. Paris 06, GRC no 04, Theranoscan, 4 rue de la Chine, F-75252 Paris, France; AP-HP, GH HUEP, Hôpital Tenon, Service d'Anatomie pathologique, 4 rue de la Chine, F-75970 Paris, France. 3. AP-HP, GH HUEP, Hôpital Tenon, Service d'Anatomie pathologique, 4 rue de la Chine, F-75970 Paris, France. 4. Plateforme de Génétique Moléculaire des Tumeurs, Pôle de Biologie et Pathologie CHU Grenoble et INSERM U 823-Institut A Bonniot-Université J Fourier, F-Grenoble, France. 5. AP-HP, GH HUEP, Hôpital Tenon, Unité de Génomique des Tumeurs Solides, Pôle de Biologie Médicale et Pathologie, 4 rue de la Chine, F-75970, Paris, France. 6. Sorbonne Universités, UPMC Univ. Paris 06, GRC no 04, Theranoscan, 4 rue de la Chine, F-75252 Paris, France; AP-HP, GH HUEP, Hôpital Tenon, Unité de Génomique des Tumeurs Solides, Pôle de Biologie Médicale et Pathologie, 4 rue de la Chine, F-75970, Paris, France. 7. Inserm, UMR-S 1172, JPARC, Team « Mucins, differentiation and epithelial carcinogenesis », Bâtiment G. Biserte, Rue Polonovski, 59045 Lille cedex, France. 8. Sorbonne Universités, UPMC Univ. Paris 06, GRC no 04, Theranoscan, 4 rue de la Chine, F-75252 Paris, France; AP-HP, GH HUEP, Hôpital Tenon, Service de Pneumologie, 4 rue de la Chine, F-75970 Paris, France. 9. Sorbonne Universités, UPMC Univ. Paris 06, GRC no 04, Theranoscan, 4 rue de la Chine, F-75252 Paris, France; AP-HP, GH HUEP, Hôpital Tenon, Service de Pneumologie, 4 rue de la Chine, F-75970 Paris, France. Electronic address: marie.wislez@tnn.aphp.fr.
Abstract
OBJECTIVES: To evaluate MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression in invasive lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA) of the lung, and the impact of oncogenic drivers. MATERIALS AND METHODS: MUC1, MUC2, MUC5B, MUC5AC, MUC6, TTF1 and Hnf4α immunohistochemistry was performed on surgical samples from 52 patients with IMA (n=25) or LPA (n=27). We searched for EGFR, KRAS, BRAF, and HER2 mutations and ALK, ROS1, and NRG1 rearrangements. RESULTS: MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression was detected in tumor cells in 77%, 2%, 63%, 36%, and 21% of cases, respectively. MUC1 was significantly more overexpressed in LPA. MUC5B, MUC5AC, and MUC6 were typically detected in goblet cells and overexpressed in IMA. Hnf4α-positive IMA (n=11) were TTF1-negative and typically did not expressed MUC1 and expressed MUC5AC and MUC6. Hnf4α-negative IMA (n=14) showed a reverse profile of mucins expression, with MUC1 expression and a lack of MUC5AC and MUC6 expression. EGFR-positive status was significantly associated with LPA, MUC1 expression, and no MUC5B, MUC5AC, or MUC6 expression. KRAS-positive status was significantly associated with IMA and MUC5B and MUC5AC expression. CONCLUSIONS: LPA and IMA exhibit specific mucin expression profiles, with MUC1 being associated with LPA, while MUC5B, MUC5AC, and MUC6 were associated with IMA. Hnf4α expression and EGFR and KRAS mutations may play a role in mucin expression profiles of these lung adenocarcinoma subtypes.
OBJECTIVES: To evaluate MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression in invasive lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA) of the lung, and the impact of oncogenic drivers. MATERIALS AND METHODS:MUC1, MUC2, MUC5B, MUC5AC, MUC6, TTF1 and Hnf4α immunohistochemistry was performed on surgical samples from 52 patients with IMA (n=25) or LPA (n=27). We searched for EGFR, KRAS, BRAF, and HER2 mutations and ALK, ROS1, and NRG1 rearrangements. RESULTS:MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression was detected in tumor cells in 77%, 2%, 63%, 36%, and 21% of cases, respectively. MUC1 was significantly more overexpressed in LPA. MUC5B, MUC5AC, and MUC6 were typically detected in goblet cells and overexpressed in IMA. Hnf4α-positive IMA (n=11) were TTF1-negative and typically did not expressed MUC1 and expressed MUC5AC and MUC6. Hnf4α-negative IMA (n=14) showed a reverse profile of mucins expression, with MUC1 expression and a lack of MUC5AC and MUC6 expression. EGFR-positive status was significantly associated with LPA, MUC1 expression, and no MUC5B, MUC5AC, or MUC6 expression. KRAS-positive status was significantly associated with IMA and MUC5B and MUC5AC expression. CONCLUSIONS:LPA and IMA exhibit specific mucin expression profiles, with MUC1 being associated with LPA, while MUC5B, MUC5AC, and MUC6 were associated with IMA. Hnf4α expression and EGFR and KRAS mutations may play a role in mucin expression profiles of these lung adenocarcinoma subtypes.
Authors: Omar Jiménez-Zarazúa; Lourdes N Vélez-Ramírez; José C Padilla-López; Juana R García-Ramírez; Pedro L González-Carillo; Jaime D Mondragón Journal: Case Rep Oncol Date: 2018-12-11