[Immunohistochemical study of breast neoplasms cells using different markers of proliferation]. / Immunogistokhimicheskoe izuchenie kletok raka molochnoi zhelezy s ispol'zovaniem raznykh markerov proliferatsii.

Proliferative activity was studied in 58 breast tumors: 10 benign tumors and 48 carcinomas 41 of which were invasive ductal carcinomas. Combined use of 3 proliferation markers (5-bromo-2-deoxyuridine, nuclear antigen of proliferating cells and Ki-67 antigen) which reflect different phases of mitotic cycle, enable determination of the S-phase index and estimation of the tumor proliferative pool as well as percentage of cells in S-phase and in mitosis and, respectively, relative duration of these phases. In breast carcinoma, S-phase is the longest phase of the mitotic cycle (45% of its duration), mitosis takes 5%. Proliferation indices when all three markers were used carry high positive correlation (r = 0.73-0.94; p < 0.000001). Proliferative activity of breast carcinoma is 5 times higher than in benign tumors and significantly increases in recurrent tumors and with growing histological malignancy of the tumor. A positive correlation exists between proliferative activity of the primary carcinoma and that of metastatic tumor in regional lymph nodes but proliferation in metastasis is, as a rule, less active than in the primary tumors. Antigen Ki-67 is the most optimal among the above proliferation markers because its expression reflects the tumor proliferative pool and its use does not require additional procedures and calculation of proliferating cells is simple and reliable.

[Comparative study of the proliferation (by detection of Ki-67 antigen) and activity of nucleolar organizer regions in breast cancer cells]. / Sravnitel'noe izuchenie proliferatsii (po vyiavleniiu antigena Ki-67) i aktivnosti iadryshkovykh organizatorov kletok raka molochnoi zhelezy.

The rates of proliferation, determined on the basis of antigen Ki-67 detection, and activity of nucleolar organizer regions (AgNORs) were compared in 10 benign lesions and 48 breast cancers (mostly invasive ductal carcinomas). Antigen Ki-67 was detected by the indirect immunoperoxidase method using polyclonal rabbit antibodies. Proteins of AgNORs were silver-stained after W.M. Howell and D.A. Black (modified by N.N.Mamayev). The fraction of Ki-67-positive cells--very close to proliferative pool--was 4.75 (1.60-11.76)% in benign tumors and 24.89 (8.64-65.16)%--in breast cancer, respectively. There was a significant correlation between Ki-67 expression and degree of histologically malignancy of breast tumors. There was a high correlation between Ki-67 expression in primary tumors and their metastases to regional lymph nodes; however, in metastases, the number of Ki-67-positive cells was significantly lower than in primary tumor. Also, the study established a distinct relationship between such indices of AgNOR activity as numbers of intra- and extranucleolar granules of silver and their total number in nucleus, on the one hand, and index of cell proliferation, on the other. The former represented specific clinicoanatomical features of tumor.

Ability of lymphocytes infiltrating breast-cancer tissue to convert androstenedione.

Lymphocytes were isolated from 43 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. In all, 23 specimens from lymphocytic-tissue infiltrates were analyzed (in some cases, material from 2 or 3 patients was combined). The ability of tumor-infiltrating lymphocytes (TIL) to convert androstenedione was demonstrated, as evaluated by hard-water release from the androgenic precursor 3H-1beta-androstenedione. In material obtained from menopausal women this ability was higher than in the women of reproductive age. A positive correlation was revealed between the level of androstenedione conversion in TIL and aromatase activity in tumor tissue, while no correlation was shown between androstenedione conversion in TIL and percentage of tumor cells in lymphocytic suspension. The data obtained suggest that factors secreted by a neoplasm are able to induce aromatase gene expression in TIL.

[Correlation between tumor tissue aromatase, histological pattern and reproductive status in patients with breast cancer]. / Sviaz' aktivnosti aromatazy v opukholevoi tkani s kharakteristikoi zabolevaniia i pokazateliami reproduktivnogo statusa u bol'nykh rakom molochnoi zhelezy.

Aromatase levels were measured in tumor tissue vis-a-vis clinico-morphological patterns of tumor, menopausal status and sex hormone concentration in blood in 50 patients with breast tumors. The test was based on heavy water release from 1 beta-3H-androstenedione. Direct correlation was established between aromatase concentration, on the one hand, and tumor size, cell differentiation status and blood-testosterone on the other. The data point to the role of aromatase concentration in situ during breast tumor genesis, its dependence on hormonal environment of tumor and its presence in breast tumor cells.

[Immunohistochemical study of the proliferation of breast cancer cells based on the expression of proliferating cell nuclear antigen (PCNA)]. / Immunogistokhimicheskoe izucheniie proliferativnoi aktivnosti kletok raka molochnoi zhelezy po ékspressii iadernogo antigena proliferiruiushchikh kletok (PCNA).

Proliferative activity was estimated in 10 benign lesions and 47 cancers of mammary gland (mainly, invasive ductal carcinomas), and 14 metastatic lymph nodes by means of immunohistochemical determination of PCNA. Total PCNA expressing nuclei (PCNAtot) and nuclei strongly stained (PCNAstr) were counted. Proliferation index (PI) measured by counting PCNAstr nuclei has a higher correlation (r = 0.94, p < 0.000000) with PI estimated by means of 5-bromo-2-desoxyuridine in vivo than that obtained by counting PCNAtot nuclei (r = 0.77, p < 0.000000). Total and strong PCNA expression increased significantly when graded according to H.J.G. Bloom & W.W. Richardson. There is a clear correlation between PI of primary breast cancer and its metastases in lymph nodes (r = 0.89, PCNAtot and r = 0.90, PCNAstr), but proliferative activity in metastases was significantly lower than that of in primary tumors (p = 0.02 and p = 0.003). PCNA expressing tumor cells is a method of evaluation of proliferative activity in tissues which permits using archival paraffin samples.

[Determination of the proliferative activity of breast cancer cells using 5-bromo-2'-deoxyuridine in vivo]. / Opredelenie proliferativnoi aktivnosti kletok raka molochnoi zhelezy s ispol'zovaniem vvedeniia 5-brom-2'-dezoksiuridina in vivo.

Proliferative activity was studied by immunohistological assay of label index (LI) involving the injection of 5-bromo-2'-deoxyuridine in vivo into 10 benign lesions and 40 breast tumors. LI level was found to be significantly higher in breast cancer patients (10.94%) than in cases of benign lesions (1.97%) (p = 0.000002). A similar relation was recorded between relapsed breast cancer (16.65%) and primary tumor (10.28%) (p = 0.03). The study also established a distinct correlation between LI of invasive ductal carcinoma and histological malignancy as determined according to Bloom and Richardson, p = 0.045 between stages I (6.03%) and II (9.60%) and p = 0.01 between stages II and III (15.37%), the ability to form tubular structures (p = 0.003), the numbers of mitoses and hyperchromatic nuclei (p = 0.006) between stages I (5.95%) and II (9.53%) and p = 0.003 between stages II and III (15.00%) and presence or absence of nuclear polymorphism (p = 0.03%). No correlation was observed between LI in breast tumor, on the one hand, and tumor size, degree of invasion, clinical stage, age, menstrual status and estrogen and progesterone receptor levels, on the other. LI in metastasis (7.07%) (15 cases) appeared to be significantly higher than in primary tumor (10.13%) (p = 0.001) and it revealed a distinct correlation with that in primary tumor (p = 0.39).

[Melanotic neuroectodermal tumor in a newborn]. / Melanoticheskaia neiroéktodermal'naia opukhol' u novorozhdennogo.

The tumor consists of two types of cells: small with abundant processes cells capable of dividing and probably being neuroblasts, and the big melanocytes forming bands and glandular-like structures. Tumor cells (mainly melanocytes) express pancytokeratins, S-100 protein, neuron-specific enolase, synaptophysin and melanin antigen. These data are the additional indication that melanotic neuroectodermal tumor is the derivative of the neural crest.