[Cowden syndrome, or multiple hamartomatous tumor syndrome, in clinical endocrinology].
Cowden syndrome (CS) is the prototypic PTEN hamartoma tumor syndromes (PHTS), rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. CS is characterized by association of macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, with increased risk for breast, thyroid and endometrial cancer. PTEN, which is located on chromosome 10q23, regulates negatively the prosurvival PI3K/Akt/mTOR pathway through a lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. CS diagnosis is clinical, based on the association of pathognomonic, major and minor criteria. The association in a patient with thyroid cancer, rarely with multinodular goiter, of typical dermatological manifestations, easily identifiable by clinical examination (papillomatous papules, acral keratoses, trichilemmomas), with a history of breast, endometrial, or renal cancer, or hamartomatous tumors presence, should alert the clinician. Clinical management of patients with CS is multidisciplinary, to include early and frequent screening, surveillance, and preventive care for associated malignancies. The development of antineoplastic agents targeting PI3K/Akt/mTOR pathway, such as rapamycin, may be the opportunity of treatment in PHTS and CS patients, for whom no specific medical treatment exist.
Sardinoux
M
M
Service des maladies endocriniennes, hôpital Lapeyronie, CHRU de Montpellier, 371, avenue du Doyen-Gaston-Giraud, 34925 Montpellier cedex 05, France. msardinoux@yahoo.fr
Raingeard
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Bessis
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D
Coupier
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I
Renard
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E
Bringer
J
J
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis; D015195:Drug Design; D016889:Endometrial Neoplasms / Q000175:diagnosis; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis* / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000175:diagnosis
D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases