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.

V-region-specific alterations of serum IgM production in multiple myeloma of IgG class.

INTRODUCTION: Multiple myeloma is accompanied by decreased polyclonal serum immunoglobulin concentrations. This suppression might be due to non-specific effects on the polyclonal lymphocyte populations as previously suggested, or it could include specific variable region-dependent mechanisms. Thus, differentiation, survival and activation to Ig secretion of B-lineage cells are dependent on the expression and signalling through the variable Ig receptor. The present study addresses the question whether such variable region-specific alterations were present in the peripheral repertoire of IgM antibodies in patients with IgG-secreting MM. MATERIALS AND METHODS: IgM reactivity repertoires towards a large panel of antigens in extracts of homologous tissues (liver, brain, stomach and heart muscle) and bacteria (Bacillus macquarensis) were analysed in sera from 22 patients diagnosed with IgG1 MM. Healthy, matched volunteers served as control donors. A modified Western assay was used, and values obtained from area integration by image analyses were submitted to multiparametric statistics. RESULTS AND CONCLUSION: The results confirm previous observations on the depression of serum IgM concentrations in multiple myeloma, and demonstrate concentration-independent, patient- and V-region-specific alterations in the polyclonal reactivity repertoires. Since the scoring of IgM reactivities by this technique is independent of IgG and because the deviations of IgM reactivity are not coincident with reactivities of (myeloma) IgG in the individual sera, the results indicate that the immunological syndrome of MM includes significant V-region-specific alterations in the polyclonal repertoires of IgM antibodies.

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.

Small-cell (oat cell) carcinoma of the endometrium.

We report a case of small-cell (oat cell) carcinoma of the endometrium in a 59-year-old woman. The tumor was confined to a portion of an adenomatous polyp. It exhibited argyrophilia with Grimelius' stain and dense-core endocrine-type granules by electron microscopy. The patient was alive and well one year later. To our knowledge, this is the fourth reported case of a small-cell carcinoma of the endometrium exhibiting endocrine differentiation.

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.

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.

[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+.

[Antigen retrieval by microwave oven with buffer of citric acid]. / Recuperación de antígenos por horno de microondas con buffer de ácido cítrico.

Microwave oven (mwo) is used to stimulate tissue fixation and to retrieve antigens damaged by fixation. Heavy metal salt solutions, water, and citric acid buffer (cab) have been suggested for this purpose. A serie of tumors treated with cab and phosphate-buffered saline (pbs) with mwo were studied immunohistochemically with 24 antibodies. Controls were treated in the same way, except for microwaving. The antibodies were directed against antigens of the following tumors: breast and prostate carcinoma, carcinoid, lymphoma and melanoma. The results showed that cab enhanced the immunoreactivity of the following antigens: estrogen receptors (AMAC), progesterone receptors (Novocastra), HMB45, vimentin, leukocyte common antigen, PCNA, p53, MIB-1 (Ki-67) and prostatic specific antigen. The antigens that did not improve their immunoreactivity, when compared with the control series were: factor VIII, keratin, Leu 22, L26, neuron-specific enolase, CEA, chromogranin, HBME-1, smooth muscle actin and EMA. Microwaving equally improved protein S100 and desmin either with cab or pbs. The only antigen that improved with pbs was actin. The results with B72.3 and NKI/C3 were poor and not reliable. In conclusion microwaving with cab enhances the immunoreactivity of the antibodies mentioned above leading to an increase in sensibility without loosing specificity.

[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.

[The immunohistochemical determination of hormonal receptors in breast cancer. A retrospective study in 322 cases]. / Determinación inmunohistoquímica de receptores hormonales en cáncer de mama. Estudio retrospectivo en 322 casos.

A study of 322 patients with infiltrating ductal carcinoma of the breast, followed from 6 to 20 years, is presented. Pathological characteristics including immunohistochemical determinations of estrogen and progesterone receptors are shown, as well as interrelations of the different factors between themselves and with the follow up. Results showed significant relations between positive estrogen receptors and low nuclear grade (p < 0.001), histological low grade (p = 0.06) and positive progesterone receptors (p = 0.001). In addition, progesterone receptors were associated with stage I (p = 0.02); tumors with less than 2 cm in diameter (p = 0.01); low nuclear grade (p < 0.001) and positive estrogen receptors (p < 0.001). The univariate Cox regression analysis of prognostic factors revealed an association between positive lymph nodes and high nuclear grade with a more frequent tumoral recurrence. On the other hand, overall survival was significantly affected by cases in stage II, positive lymph nodes, tumors with diameter greater than 2 cm, and high nuclear grade. Stepwise Cox regression analysis showed that a high nuclear grade, positive lymph nodes and absence of estrogen receptor, were associated with a higher risk for recurrence and that tumor size and the state of lymph nodes were predictive for overall survival. This paper demonstrates that histochemical determination of hormonal receptors is useful because together with other known prognostic factors it contributes to a better management of patients with breast carcinoma.

[Expression of p53 in gastric carcinoma. Prognostic value]. / Expresión de p53 en el carcinoma gástrico. Su valor pronóstico.

P53 gene mutation has been described with variable frequency in gastric cancer and its biological significance remains unclear. We studied 101 gastric carcinomas to evaluate the association between this genetic alteration and the evolution of gastric cancer. Of these, 67 patients were men and 34 were women. The median age at diagnosis was 68 years. The tumors were obtained from gastrectomies. The p53 gene mutation was determined with the monoclonal antibody DO7 (Novocastra). The neoplasms were classified as tumors with high or low level p53 expression according to the intensity and distribution of the nuclear staining. Forty eight tumors showed high level of p53 immunoreactivity. The association of p53 expression with age, sex, tumor size, histologic type, histologic grade, depth of invasion, localization, lymph node metastases, type of surgery and 5 year survival rate was investigated. The results did not demonstrate any significant association between p53 expression and the factors mentioned above.

[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.

[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.

[Idiopathic hypophysitis in elderly patients. Report of 2 cases and review of literature]. / Hipofisitis idiopática en pacientes de edad avanzada. Presentación de dos casos y revisión de la literatura.

INTRODUCTION: Hypophysis inflammatory tumors are a non frequent cause for hypopituitarism. The motive of outpatient visit is headache. It is more frequent in pregnancy and immediate post-labor women. The pathology shows a lymphocytic inflammatory infiltrated or granulomas with giant cells (these can be accompanied with an infectious or autoimmune systemic disease associated). CLINICAL CASES: We present two elderly female patients, without infectious or autoimmune pathology associated, with suggestive abnormalities of hypophysial adenoma by MRI. Both presented a suspecting clinical manifestation of intracranial expansive lesion (progressive intensive headaches, with partial compromise of the III left pair in the second one), noticing by laboratory a subclinical hormonal dysfunction. Surgery of tumoral exeresis was underwent in both patients, showing a granulomatous hypophysitis in one and a lymphocytic hypophysitis in the other. CONCLUSION: Hypophysis inflammatory tumors must be considered as a preoperative differential diagnosis of every hypophysial tumor without important hormonal dysfunction associated, mainly in women and what is more in pregnancy or lying-in women, taking into account that surgery of tumoral resection can worsen a subclinic hypophysial dysfunction.

[MMP-2 expression (type IV collagenase) in gastric cancer]. / Expresión de MMP-2 (colagenasa tipo IV) en el carcinoma gástrico.

The protein MMP-2 (type IV collagenase) belongs to the family of metalloproteinases. Its function is related to cellular matrix degradation including basement membrane type IV collagen. Its presence in the neoplastic cells might enhance its capacity for dissemination. To find out some of its clinico-pathological and immunohistochemical behavior, 98 adenocarcinomas of the stomach were immunohistochemically studied, in search for MMP-2 in neoplastic cells. The results showed a correlation between MMP-2 with parietal depth of infiltration (p = 0.03) and with metastases in regional lymph nodes (p = 0.05). On the other hand, no correlation was found with sex, gastric localization, size of the tumor, histological type or grade neither with expression of MIB-1, c-erbB-2 nor p53 proteins, recurrence nor 5 year survival or no recurrency.

[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.