Cytohistologic correlation of nuclear grade in breast carcinoma.

OBJECTIVE: To compare the nuclear grade (NG) in cytologic material (CNG) obtained from breast fine needle aspiration biopsies (FNABs) with the NG observed in surgical biopsies (BNG) of the same tumors. STUDY DESIGN: The study group consisted of 135 breast carcinomas with both FNAB and biopsy. Most of them were invasive ductal carcinomas. Cytologic aspirates and tissue sections were graded simultaneously by the three authors using a multiheaded microscope. Fisher's modification of Black's nuclear grading scheme was used. RESULTS: There was agreement between CNG and BNG in 70.37% of tumors. The percentage coincidence was slightly greater for NG 3. CONCLUSION: Nuclear grade can be easily established on FNAB. The lack of correlation (29.63%) may have been due to tumor heterogeneity and observer subjectivity when assigning nuclear grade.

[Expression of p53 and bcl-2 in colorectal adenomas and carcinomas]. / Expresión de p53 y de bcl-2 en adenomas y carcinomas colorrectales.

Recent publications have associated p53 and bcl-2 genes in the process of neoplastic transformation. As the colonic adenoma-carcinoma sequence is an adequate natural model for carcinogenesis, it was considered interesting to analyze the expression of bcl-2 and p53 in these neoplasms. Seventy three adenomatous polyps (adenomas) and 60 adenocarcinomas of the colon and rectum were studied. Adenomas showed mild dysplasia in 16, moderate in 27, severe in 15 and focal carcinoma in the remaining 15. Adenocarcinomas surpassed the deep muscle layer in every case and were moderately differentiated. The studied gene expression was analized immunohistochemically using antibodies bcl-2 from Dako and p53 from Novocastra, both at a 1:100 dilution. Cytoplasmic stain for bcl-2 and nuclear stain for p53 above 10% of the cells were considered positive for each gene respectively. Results showed that there was accumulation of p53 protein in 26/58 (45%) adenomas with different grades of dysplasia. This result is similar to the reactivity found in adenomas with focal carcinoma where 8/15 (53%, p = 0.4) were positive but different from adenocarcinomas which were positive in 47/60 (78%, p = 0.0001). Regarding bcl-2, positivity was found in 53/73 (73%) of all the adenomas whereas adenocarcinoma showed expression in 14/60 (23%, p = 0.0000). When adenomas were grouped according to their degree of dysplasia and the existence of focal carcinoma, a diminishing frequency of reactivity for bcl-2 was found and when adenomas with three different grades of dysplasia were fused together, 47/58 (81%) were positive and this was compared with adenomas having focal carcinoma, 6/15 (40%) and with adenocarcinoma, 14/60 (23%), they showed significant differences (p = 0.001 and p = 0.0000 respectively). The analysis of the frequency of expression for both genes studied in the different lesions described yielded an inverse relation between them. This study allows the conclusion that the expression of bcl-2 is an early event in carcinogenesis and that it is replaced by mutation of p53 as the neoplastic change progresses.

Carcinoembryonic antigen expression in stages I and II breast cancer: its relationship with clinicopathologic factors.

Carcinoembryonic antigen (CEA) has been detected by immunohistochemistry in breast carcinoma, but its relationship with prognosis is still unclear. This difficulty may be because of the great variety of antibodies used for its determination. In the present study, 271 stages I and II breast carcinomas are analyzed by immunohistochemistry, using T84.66 antibody, a well-known highly specific CEA antibody. The results show that CEA expression was not associated with any of the clinicopathologic factors analyzed. Factors associated with disease-free survival (DFS) after univariate logistic regression analyses were tumor size smaller than 2 cm (P = .01), lymph node free of metastases (P = .0000), low nuclear grade (P = .007), absence of c-erbB-2 overexpression (P = .02), and bcl-2 (P = .005) and CEA expression (P = .005), whereas those significantly associated with a better overall survival (OS) were tumor size small than 2 cm (P = .002), lymph node free of metastases (P = .0001), low nuclear grade (P = .01), low histological grade (P = .02), absence of c-erbB-2 overexpression (P = .002) and bcl-2 expression (P = .01). After multivariate stepwise regression analysis, lymph node free of metastases (P = .0000), CEA expression (P = .001), absence of c-erbB-2 overexpression (P = .01), and bcl-2 expression (P = .01) were found to be independent factors associated with DFS, whereas lymph node free of metastases (P = .0000), tumor size smaller than 2 cm (P = .0000), and absence of c-erbB-2 overexpression (P = .004) were associated with a better OS. These results show that immunohistochemical detection of CEA with the antibody T84.66 may be useful as an additional factor in establishing breast cancer prognosis.

[Immunohistochemical characteristics of mammary carcinomas with estrogen-negative and progesterone-positive receptors]. / Características de los carcinomas de mama receptores de estrógenos negativos y receptores de progesterona positivos determinados por inmunohistoquímica.

In a series of 256 mammary carcinomas, 22 (8.5%) were positive for progesterone receptors (PR) and negative for estrogen receptors (ER). These cases seem to belong to a distinctive group with a biologic behavior not well understood. In order to contribute to a better understanding of such tumors, their association with different pathologic and immunohistochemical factors were compared with those of the rest of the tumors of the series. The results were that favorable factors such as smaller size, negative axillary lymph nodes and low histologic and nuclear grades were decreasingly associated with tumors that were ER+ PR+; ER+ PR-; ER- PR+; and ER- PR-. In relation to immunohistochemical features, tumors that were ER+ PR+; ER+ PR- and ER- PR+ behaved in a similar way, whereas ER- PR- tumors were different from the rest because fewer expressed bcl-2 (p = 0.0000) and had a greater expression for p53 (p = 0.009) and MIB-1/Ki-67 (p = 0.05). No significant differences were found between the four populations in recurrence rate or metastases, nor overall survival. In conclusion, these findings show that tumors that are ER- PR+ might have biological characteristics somewhere in between ER+ PR+ and ER- PR+.

[Reproducibility of nuclear grade in breast neoplasm. A multicenter experience]. / Reproducibilidad del grado nuclear en el cáncer de mama. Una experiencia multicéntrica.

Nuclear grade is considered a valuable prognostic factor in mammary carcinomas. Since the histological diagnosis of most of these tumors is made by "non expert" pathologists, it was considered interesting to find out the reproducibility of general pathologists to define the nuclear grade. In order to do this, a series of 15 mammary carcinomas, 10 of them randomly selected and 5 because they were considered difficult to classify for nuclear grade, were examined separately by 10 general pathologists. In a first round of observation, each one of them graded the cases according to their own criteria as used routinely, and for a second round they followed a written guide. An analysis of variance was applied to the data and no significant differences were found between observers, neither in the randomly selected cases nor in the total series. The written guide, surprisingly, instead of lowering the differences, increased them. Analysis of the individual performance of observers showed two of them having a great variation between both rounds of observation, and this was considered to influence the results of the whole group. Interobserver performance to discriminate high grade tumors (G3) from the rest, showed a good correlation in all the participants. These results allow us to conclude that in this series, examined by general pathologists, an acceptable reproducibility was observed, specially when high risk tumors were being identified.

Diagnostic value of p53 protein in the study of serous effusions.

The differential diagnosis between neoplastic and reactive mesothelial cells is one of the most frequent problems in the study of serous effusions. We assessed the utility of the immunohistochemical determination of p53 protein as a marker of malignancy in 34 embedded blocks of neoplastic fluids and 30 nonneoplastic effusions. Eleven (32.4%) of the tumor fluids were positive for this antibody, while all the nonneoplastic fluids were negative. A specificity of 100% and a sensitivity of 59% were observed. The immunohistochemical determination of p53 protein seems to be helpful in the differential diagnosis of effusions; its principal limitation is its relatively low sensitivity.

[Expression of MIB-1/KI-67 and bcl-2 in gastric carcinoma. Relationship with clinico-pathological factors]. / Expresion de MIB-1/KI-67 y de bcl-2 en el carcinoma gástrico. Relación con factores clínico-patológicos.

Neoplastic development partly depends on a balance between cellular proliferative activity and the eventual suppression of the mechanism of apoptosis. Proliferative activity can be estimated by quantification of KI-67 antigen that appears during phases G1, S, G2 and M of the cellular cycle, whereas apoptosis is shown by the expression of the bcl-2 protein. In this study the expression of KI-67 and bcl-2 antigens was examined in a series of 97 gastric adenocarcinomas, to find out their relations with different clinical and pathological factors. The results showed that the expression of KI-67 was only associated to histological grade and did not have any prognostic significance. On the other hand, there was a better 5 year survival rate when invasion did not go beyond the muscularis propria, there were no lymph node metastases, in the woman and when tumors were located in the antrum. bcl-2 protein was surprisingly negative in all cases albeit of previous descriptions of overexpression of this protein in cases of gastric dysplasia. It is postulated that expression of bcl-2 could appear at an early stage of gastric carcinogenesis and that only a small proportion of malignant tumors would maintain that overexpression.

Expresion de MIB-1/KI-67 y de bcl-2 en el carcinoma gástrico. Relación con factores clínico-patológicos. / [Expression of MIB-1/KI-67 and bcl-2 in gastric carcinoma. Relationship with clinico-pathological factors]

Neoplastic development partly depends on a balance between cellular proliferative activity and the eventual suppression of the mechanism of apoptosis. Proliferative activity can be estimated by quantification of KI-67 antigen that appears during phases G1, S, G2 and M of the cellular cycle, whereas apoptosis is shown by the expression of the bcl-2 protein. In this study the expression of KI-67 and bcl-2 antigens was examined in a series of 97 gastric adenocarcinomas, to find out their relations with different clinical and pathological factors. The results showed that the expression of KI-67 was only associated to histological grade and did not have any prognostic significance. On the other hand, there was a better 5 year survival rate when invasion did not go beyond the muscularis propria, there were no lymph node metastases, in the woman and when tumors were located in the antrum. bcl-2 protein was surprisingly negative in all cases albeit of previous descriptions of overexpression of this protein in cases of gastric dysplasia. It is postulated that expression of bcl-2 could appear at an early stage of gastric carcinogenesis and that only a small proportion of malignant tumors would maintain that overexpression.

A simplified multitissue block.

Multitissue blocks are rapidly gaining acceptance as useful control materials for the immunohistochemistry laboratory. Moreover, they may be conveniently and economically used to screen antibodies and optimize the assay conditions. Several schemes of preparation of multitissue blocks have been proposed. The author describes an improved method for preparing multitissue blocks; this method requires no special equipment or skills.

Cáncer gástrico: características clinico-patológicas y expresión del oncogen c-erbB-2 en 122 casos / Gastric cancer: clinico-pathological characteristics and expression of c-erbB-2 oncogen in 122 cases

Se presenta una serie de 119 pacientes com 122 carcinomas gástricos tratados con gastrectomía y con seguimento mayor de 5 años. Eran 80 (67,2 por ciento) hombres y 39 (32,8 por ciento) mujeres con una edad promedio general de 66,4 años. En 101 (84,9 por ciento) se hizo diagnóstico endoscópico de cáncer. El dolor fue el síntoma más frecuente (55,5 por ciento). Setenta y dos (59 por ciento) estaban localizados en el antro, 26 (21 por ciento) en cardias y 24 (19,7 por ciento) en el cuerpo. El 43,4 por ciento medía menos de 5 cm y el 56,6 por ciento, 5 o más cm. Ochenta y nueve (73 por ciento) eran de tipo intestinal, 15 (12,3 por ciento) difuso, y 18 (14,8 por ciento mixto. Ochenta (65,6 por ciento) eran de grado histológico bajo y 42 (34,4 por ciento) alto. Diez (9,2 por ciento) fueron tempranos y 112 (91,8 por ciento) avanzados. Se observó amplificación del oncogen c-erbB-2 en 13 (10,6 por ciento). La amplificación del c-erbB-2 mostró una asociación estadísticamente significativa con los tumores menores de 5 cm (p = 0,05) y con los de grado histológico bajo. La sobrevida a 5 años se correlacionó con tumores menores de 5 cm, con invasión de la pared sin sobrepasar la muscular propia y con ganglios libres de metástasis. No se encontró asociación entre la amplificación del c-erbB-2 y la sobrevida (AU)

Cáncer gástrico: características clinico-patológicas y expresión del oncogen c-erbB-2 en 122 casos / Gastric cancer: clinico-pathological characteristics and expression of c-erbB-2 oncogen in 122 cases

Se presenta una serie de 119 pacientes com 122 carcinomas gástricos tratados con gastrectomía y con seguimento mayor de 5 años. Eran 80 (67,2 por ciento) hombres y 39 (32,8 por ciento) mujeres con una edad promedio general de 66,4 años. En 101 (84,9 por ciento) se hizo diagnóstico endoscópico de cáncer. El dolor fue el síntoma más frecuente (55,5 por ciento). Setenta y dos (59 por ciento) estaban localizados en el antro, 26 (21 por ciento) en cardias y 24 (19,7 por ciento) en el cuerpo. El 43,4 por ciento medía menos de 5 cm y el 56,6 por ciento, 5 o más cm. Ochenta y nueve (73 por ciento) eran de tipo intestinal, 15 (12,3 por ciento) difuso, y 18 (14,8 por ciento mixto. Ochenta (65,6 por ciento) eran de grado histológico bajo y 42 (34,4 por ciento) alto. Diez (9,2 por ciento) fueron tempranos y 112 (91,8 por ciento) avanzados. Se observó amplificación del oncogen c-erbB-2 en 13 (10,6 por ciento). La amplificación del c-erbB-2 mostró una asociación estadísticamente significativa con los tumores menores de 5 cm (p = 0,05) y con los de grado histológico bajo. La sobrevida a 5 años se correlacionó con tumores menores de 5 cm, con invasión de la pared sin sobrepasar la muscular propia y con ganglios libres de metástasis. No se encontró asociación entre la amplificación del c-erbB-2 y la sobrevida

[Gastric cancer. Clinico-pathological characteristics and expression of c-erB-2 oncogene in 122 cases]. / Cáncer gástrico. Características clinico-patológicas y expresión del oncogen c-erbB-2 en 122 casos.

A series of 119 patients with 122 gastric carcinomas treated by gastrectomy, with a follow up of more than 5 years is presented. There were 80 (67.2%) men and 39 (32.8%) women with a mean age of 66.4 years. In 101 (84.9%) the diagnosis of cancer was endoscopic. Pain was the most frequent symptom (55.5%). Seventy two (59%) were localized in the antrum; 26 (21%) were cardial, and 24 (19.7%) were in the body. In 43.4% the size was smaller than 5 cm and in 56.6% it measured 5 cm or more. Eighty nine (73%) were of the intestinal type, 15 (12.3%) were diffuse and 18 (14.8%) were mixed. Eighty (65.6%) were low histological grade and 42 (34.4%) were high grade. Ten (9.2%) were early carcinomas and 112 (91.8%) advanced carcinomas. An amplification of the c-erbB-2 oncogene was associated with tumors that were smaller than 5 cm (p = 0.05) and with histological low grade (p = 0.005). A five years survival correlated with tumors smaller than 5 cm (p = 0.02), with parietal infiltration not surpassing the muscular layer (p = 0.001), and without lymph node metastases (p = 0.001). There was no association between survival and amplification of c-erbB-2 oncogene.

Cáncer gástrico. Características clinico-patológicas y expresión del oncogen c-erbB-2 en 122 casos. / [Gastric cancer. Clinico-pathological characteristics and expression of c-erB-2 oncogene in 122 cases]

A series of 119 patients with 122 gastric carcinomas treated by gastrectomy, with a follow up of more than 5 years is presented. There were 80 (67.2

) men and 39 (32.8

) women with a mean age of 66.4 years. In 101 (84.9

) the diagnosis of cancer was endoscopic. Pain was the most frequent symptom (55.5

). Seventy two (59

) were localized in the antrum; 26 (21

) were cardial, and 24 (19.7

) were in the body. In 43.4

the size was smaller than 5 cm and in 56.6

it measured 5 cm or more. Eighty nine (73

) were of the intestinal type, 15 (12.3

) were diffuse and 18 (14.8

) were mixed. Eighty (65.6

) were low histological grade and 42 (34.4

) were high grade. Ten (9.2

) were early carcinomas and 112 (91.8

) advanced carcinomas. An amplification of the c-erbB-2 oncogene was associated with tumors that were smaller than 5 cm (p = 0.05) and with histological low grade (p = 0.005). A five years survival correlated with tumors smaller than 5 cm (p = 0.02), with parietal infiltration not surpassing the muscular layer (p = 0.001), and without lymph node metastases (p = 0.001). There was no association between survival and amplification of c-erbB-2 oncogene.