Browsing by Author "Majerson, Alejandro"
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- ItemMismatch repair expression in testicular cancer predicts recurrence and survival(WILEY-LISS, 2008) Velasco, Alfredo; Corvalan, Alejandro; Wistuba, Ignacio I.; Riquelme, Erick; Chuaqui, Rodrigo; Majerson, Alejandro; Leach, Fredrick S.We investigated mismatch repair (MMR) gene expression in testicular cancer as a molecular marker for clinical outcome (recurrence, response to chemotherapy and death) using protein expression and specific genetic alterations associated with the presence or absence of MMR activity. One hundred sixty-two cases of paraffin-embedded testis cancer specimens were subjected to immunohistochemical analysis using monoclonal antibody for MLH1 and MSH2 MMR proteins and genetic analysis using specific polymorphic markers. The degree of MMR immunoreactivity and genetic instability in the form of loss of heterozygosity (LOH) and/or microsatellite instability (MSI) were determined by comparing matched normal and tumor tissue. The degree of immunohistochemical staining for MMR expression was associated with a shorter time to tumor recurrence, resistance to chemotherapy and death. Furthermore, clinical relapse and cancer specific death was also associated with tumors exhibiting a high degree of MSI, p = 0.01 and 0.04, respectively. In contrast, LOH was not associated with recurrence, resistance to chemotherapy or death. Therefore, MMR expression defines testis cancers with distinct molecular properties and clinical behavior, such that tumors with decreased MMR immunostaining and/or increased frequency of MSI have a shorter time to recurrence and death despite chemotherapy. (c) 2007 Wiley-Liss, Inc.
- ItemThe Spectrum from Overt Primary Aldosteronism to Mild Dysregulated Aldosterone Production in Incidentally Discovered Adrenocortical Adenomas(2024) Uslar Nawrath, Thomas Hermann; Olmos, Roberto; Burnier, Alberth; Sanfuentes, Benjamín; Böhm, Pauline; Orellana, Maria Paz; Guarda, Francisco J.; Huete, Alvaro; Mertens, Nicolás; Besa, Cecilia; Andia, Marcelo E.; Majerson, Alejandro; Cartes, Jaime; Fardella, Carlos; Allende, Fidel; Solari, Sandra; Vaidya, Anand; Baudrand Biggs, RenéBackground Incidental adrenocortical adenomas (IA) are common. Current guidelines suggest screening for primary aldosteronism (PA) only in cases of hypertension or hypokalemia. This study aimed to evaluate the spectrum from overt PA to mild dysregulated aldosterone production with a sensitive protocol irrespective of blood pressure (BP) and potassium in patients with IA.Methods 254 consecutive patients (excluding hypercortisolism) were evaluated. The spectrum of PA was defined as a suppressed renin plus the following criteria: 1)Overt PA: aldosterone-to-renin-ratio (ARR) >30 ng/dL-to-ng/mL/hr, plasma aldosterone concentration (PAC) >15ng/dL, and/or 24h urinary aldosterone >10 ug/24h; 2)Moderate PA: ARR 20-30 ng/dL-to-ng/mL/hr, PAC 10-15 ng/dL; 3)Mild dysregulated aldosterone production: ARR <20 ng/dL-to-ng/mL/hr and PAC >5-10 ng/dL.Results 35% (n=89/254) met criteria for PA spectrum, 20% (34/89) were initially normotensive and 94% (84/89) normokalemic. Overt, moderate, and mild groups were 10%, 12%, and 13%. There were trends across groups of clinical severity: systolic BP (153±19, 140±14, 137±14 mmHg, p-trend<0.05), resistant hypertension (50%, 23%, 7% p-trend=<0.001), daily defined dose of antihypertensives (DDD) (3.2±1.6, 1.2±1.5, 0.4±0.6 p-trend=0.001), and lower eGFR (75.5±30.8, 97.8±38.5, 101±25.5, p-trend<0.01). At follow-up (mean 28±15 months), 87% had treatment with MR antagonists or surgery with decreased systolic BP relative to clinical severity, −31.3 ±23, −12.7 ±19, and −11.4 ±19 mmHg, (p-trend<0.001). Similar trends were observed for DDD, with significant increase in renin.Conclusions There is a prevalent spectrum of clinically-relevant PA and dysregulated aldosterone production in IA, irrespective of BP or potassium, usually undetected. Aldosterone-directed treatment improved BP and normalized renin even in milder cases.