Guia Vannucchi1, Simone De Leo2, Michela Perrino2, Stefania Rossi2, Delfina Tosi2, Valentina Cirello2, Carla Colombo2, Gaetano Bulfamante3, Leonardo Vicentini2, Laura Fugazzola3. 1. Endocrine UnitPadiglione Granelli, Fondazione IRCCS Ca' Granda, Via F. Sforza, 35, 20122 Milan, ItalyDepartment of Clinical Sciences and Community HealthUniversity of Milan, Milan, ItalyDivision of PathologySan Paolo Hospital, Milan, ItalyDepartments of Health SciencesPathophysiology and TransplantationUniversity of Milan, Milan, ItalyEndocrine Surgery UnitFondazione IRCCS Ca' Granda, Milan, Italy guiava@libero.it. 2. Endocrine UnitPadiglione Granelli, Fondazione IRCCS Ca' Granda, Via F. Sforza, 35, 20122 Milan, ItalyDepartment of Clinical Sciences and Community HealthUniversity of Milan, Milan, ItalyDivision of PathologySan Paolo Hospital, Milan, ItalyDepartments of Health SciencesPathophysiology and TransplantationUniversity of Milan, Milan, ItalyEndocrine Surgery UnitFondazione IRCCS Ca' Granda, Milan, Italy. 3. Endocrine UnitPadiglione Granelli, Fondazione IRCCS Ca' Granda, Via F. Sforza, 35, 20122 Milan, ItalyDepartment of Clinical Sciences and Community HealthUniversity of Milan, Milan, ItalyDivision of PathologySan Paolo Hospital, Milan, ItalyDepartments of Health SciencesPathophysiology and TransplantationUniversity of Milan, Milan, ItalyEndocrine Surgery UnitFondazione IRCCS Ca' Granda, Milan, Italy Endocrine UnitPadiglione Granelli, Fondazione IRCCS Ca' Granda, Via F. Sforza, 35, 20122 Milan, ItalyDepartment of Clinical Sciences and Community HealthUniversity of Milan, Milan, ItalyDivision of PathologySan Paolo Hospital, Milan, ItalyDepartments of Health SciencesPathophysiology and TransplantationUniversity of Milan, Milan, ItalyEndocrine Surgery UnitFondazione IRCCS Ca' Granda, Milan, Italy.
Abstract
BACKGROUND: Thyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors. METHODS: We studied the expression of estrogen receptor α (ERα or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features. RESULTS: ERα and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER- and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the 'receptor conversion' phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ERα-positive primary tumors analyzed had ERα-negative metastatic lymph nodes. At the genetic analyses, BRAF(V600E) mutation was detected in 23.2% of the tumors and had a higher prevalence in larger tumors and in those with a stronger ERα or PR staining. CONCLUSIONS: The whole of the findings reported in the present study argue for an association between ERα and PR sex hormone receptor expression and a more aggressive presentation. Although no impact on outcome was found, the evaluation of ERα and PR receptor expression could add insights into the biological behavior of tumors and could modify the follow-up, particularly in fertile women affected with persistent disease.
BACKGROUND: Thyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors. METHODS: We studied the expression of estrogen receptor α (ERα or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features. RESULTS: ERα and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER- and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the 'receptor conversion' phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ERα-positive primary tumors analyzed had ERα-negative metastatic lymph nodes. At the genetic analyses, BRAF(V600E) mutation was detected in 23.2% of the tumors and had a higher prevalence in larger tumors and in those with a stronger ERα or PR staining. CONCLUSIONS: The whole of the findings reported in the present study argue for an association between ERα and PR sex hormone receptor expression and a more aggressive presentation. Although no impact on outcome was found, the evaluation of ERα and PR receptor expression could add insights into the biological behavior of tumors and could modify the follow-up, particularly in fertile women affected with persistent disease.
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