BACKGROUND: It is poorly described how endometrial cancer biology changes during tumor evolution. We hypothesize that characterization of molecular targets in recurrent lesions is more relevant for targeting treatment. METHODS: Paired biopsies from primary and recurrent endometrial cancer tumors (n = 85) were stained immunohistochemically for the following proteins: estrogen receptor (ER), progesterone receptor (PR), stathmin (correlating with phosphatidylinositol 3-kinase activity), HER-2/neu, WT1 (Wilms tumor gene 1), phospho-mammalian target of rapamycin (p-mTOR), and p53. Each tumor was scored, using a semiquantitative and subjective grading system. Discordance, a change in expression between primary and recurrent tumor, was defined as ≥ 2 step change; concordance was ≤ 1 step change. The frequency of change was correlated with established prognostic markers in endometrial cancer. RESULTS: Fifty-six patients (67%) were diagnosed with endometrioid carcinoma, 23 (27%) with serous/clear cell carcinoma. A change in expression between primary and recurrent tumor was noted in 7% to 31% of patients for ER, PR, stathmin, HER-2/neu, WT1, p-mTOR, and p53. Concordant-positive cases for PR were significantly correlated with stage, tumor grade, and histological subtype. Expression of ER, p53, and p-mTOR in cytoplasm in the recurrent tumor correlated significantly with survival. CONCLUSIONS: Endometrial cancer biology changes over time. The decision on targeted treatment should preferably be based on recurrent tumor characteristics.
BACKGROUND: It is poorly described how endometrial cancer biology changes during tumor evolution. We hypothesize that characterization of molecular targets in recurrent lesions is more relevant for targeting treatment. METHODS: Paired biopsies from primary and recurrent endometrial cancer tumors (n = 85) were stained immunohistochemically for the following proteins: estrogen receptor (ER), progesterone receptor (PR), stathmin (correlating with phosphatidylinositol 3-kinase activity), HER-2/neu, WT1 (Wilms tumor gene 1), phospho-mammalian target of rapamycin (p-mTOR), and p53. Each tumor was scored, using a semiquantitative and subjective grading system. Discordance, a change in expression between primary and recurrent tumor, was defined as ≥ 2 step change; concordance was ≤ 1 step change. The frequency of change was correlated with established prognostic markers in endometrial cancer. RESULTS: Fifty-six patients (67%) were diagnosed with endometrioid carcinoma, 23 (27%) with serous/clear cell carcinoma. A change in expression between primary and recurrent tumor was noted in 7% to 31% of patients for ER, PR, stathmin, HER-2/neu, WT1, p-mTOR, and p53. Concordant-positive cases for PR were significantly correlated with stage, tumor grade, and histological subtype. Expression of ER, p53, and p-mTOR in cytoplasm in the recurrent tumor correlated significantly with survival. CONCLUSIONS:Endometrial cancer biology changes over time. The decision on targeted treatment should preferably be based on recurrent tumor characteristics.
Authors: Henry D Reyes; Jeffrey Miecznikowski; Jesus Gonzalez-Bosquet; Eric J Devor; Yuping Zhang; Kristina W Thiel; Megan I Samuelson; Megan McDonald; Jean-Marie Stephan; Parviz Hanjani; Saketh Guntupalli; Krishnansu S Tewari; Floor Backes; Nilsa Ramirez; Gini F Fleming; Virginia Filiaci; Michael J Birrer; Kimberly K Leslie Journal: Gynecol Oncol Date: 2017-05-19 Impact factor: 5.482
Authors: Neesha C Dhani; Hal W Hirte; Lisa Wang; Julia V Burnier; Angela Jain; Marcus O Butler; Stephen Welch; Gini F Fleming; Jean Hurteau; Koji Matsuo; Daniela Matei; Waldo Jimenez; Carolyn Johnston; Mihaela Cristea; Katia Tonkin; Prafull Ghatage; Stephanie Lheureux; Anjali Mehta; Judy Quintos; Qian Tan; Suzanne Kamel-Reid; Olga Ludkovski; Ming-Sound Tsao; John J Wright; Amit M Oza Journal: Clin Cancer Res Date: 2020-01-28 Impact factor: 12.531
Authors: Henrica M J Werner; Jone Trovik; Mari K Halle; Elisabeth Wik; Lars A Akslen; Even Birkeland; Therese Bredholt; Ingvild L Tangen; Camilla Krakstad; Helga B Salvesen Journal: PLoS One Date: 2014-02-25 Impact factor: 3.240