Progesterone induction of mammary carcinomas in BALB/c female mice. Correlation between progestin dependence and morphology.

We have demonstrated that medroxyprogesterone acetate (MPA), when administered in high doses, induces mammary carcinomas in virgin female BALB/c mice. Since one of the possible explanations for this effect was its progestagenic effects, we decided to investigate whether progesterone (Pg) alone could also induce mammary adenocarcinomas in our model and if MPA at doses lower than those used to establish the model was also carcinogenic. A total of 136 mice were subdivided into 3 groups: Group 1, 44 mice were implanted s.c. with 40 mg Pg silastic pellets at the beginning of the experiment, and 6 months later with a 20 mg Pg pellet; Group 2, 45 mice were similarly treated with MPA pellets; Group 3, 47 mice were inoculated s.c. with 40 mg MPA every three months. At the end of 20 months, 9 animals had developed mammary tumors in Group 1, 18 in Group 2 and 34 in Group 3 (actuarial incidence = 28%, 58%, and 98%, respectively); tumor latency was similar in all groups: 46.2 +/- 13.1, 51.3 +/- 9.9, and 50.1 +/- 2.1 weeks, respectively. Seven (Group 1), 14 (Group 2), and 25 (Group 3) tumors were transplanted into syngeneic mice to determine progestin dependence. All tumors, except one from Group 1, were histologically characterized. In Group 1 (Pg 60 mg), 4 tumors (67%) were infiltrating lobular carcinomas and 2 were ductal carcinomas (33%). In Group 2 (MPA 60 mg), 2 tumors (14%) were lobular and 12 were ductal adenocarcinomas (86%) (Group 1 vs Group 2: p < 0.05), whereas in Group 3 (MPA 160 mg), 8 were lobular carcinomas (32%) and 17 were ductal carcinomas (68%). In syngeneic passages all lobular tumors behaved as progestin independent (PI) and ductal tumors as progestin dependent (PD). All ductal tumors, except one, expressed estrogen receptors (ER) and progesterone receptors (PR), whereas receptor expression was variable in lobular carcinomas. It can be concluded that Pg induces mostly lobular, PI mammary tumors in BALB/c female mice. The fact that most MPA-induced tumors are ductal and PD suggests that the two hormones use different carcinogenic pathways.

Amplificación y rearreglo in vivo del oncogen c-myc en tumores de mama humano / Entargement and read justment in vivo of the c-myc oncogene in tumors of human breast

Hemos estudiado la organozación genómica del proto-oncogen myc celular (c-myc) en 48 tumores de mama primarios de humano. Dos tipos de alteraciones (amplificación y rearreglo) se observó en 27 de los tumores estudiados (56%). El proto-oncogen c-myc, apareció amplificado de 2 a 15 veces en el DNA de 20 tumores (41%). Fragmentos relacionados a c-myc no germinal (rearreglos) de tamaño variable fueron detectados en 7 tumores de mama primarios (6 malignos, 1 benigno); 4 de estos tumores presentaron tanto arreglo como amplificación y los otros 3 presentaron únicamente rearreglo. La mayoría de los tumores analizados fueron adenocarcinomas ductal invasivo; 58% de éstos mostraron alteraciones genéticas en el locus c-myc. Aunque las alteraciones de c-myc descritas aquí no aparecen correlacionarse con el comportamiento agresivo de los tumores de mama primarios, parecen estar asociados con el desarrollo de carcinoma mamario

Ultraestructura del carcinoma intraductal de la mama / Ultrastructure of intraduct carcinoma of the mamary gland

Se estudiaron 2 casos de carcinoma intraductal de la mama y 2 casos de carcinoma microinfiltrante, se destacaron el valor de la unión epitelioestromal y la presencia o no de los miofibroblastos en el estroma. En el carcinoma intraductal la lámina basal puede estar intacta, con brechas o haber desaparecido, pero el criterio más seguro es que esté intacta; en el estroma hay fibroblastos con el retículo endoplasmático dilatado, pero no hay miofibroblastos. En el carcinoma microinfiltrante, además de la brechas o desaparición de la lámina, hay salida o protusión de las células carcinomatosas hacia el estroma y presencia de miofibroblastos