Benign Tumor Tissues Research Articles

Histamine synthesis and content in benign and malignant breast tumours. Its effects on other host tissues.

We studied 100 patients: 40 with breast cancer, 41 with benign breast tumours and 19 non-cancer-bearing cholecystectomy patients, in order to measure the histidine decarboxylase activity and histamine content in benign and malignant breast tumours, and to determine whether the histamine metabolism affected skin and muscle tissue distant from the tumour. The HDC-activity of cancerous tissue was significantly higher (P < 0.01) than that registered in the healthy mammary gland tissue of the same patient, being even more pronounced in benign tumour tissue (P < 0.001). However, the histamine content was found to be significantly lower (P < 0.01) in malignant tumours, but higher in benign tumoural tissue as compared with the healthy tissue of the same patient. We also found that the histamine content in muscle tissue was significantly higher in cancer patients than in non-cancer patients. These findings highlight the fact that intracellular histamine metabolism varies in benign and malignant tumours, and that high histamine synthesis of malignant tumours affects other host tissue.

Can patients with benign breast disease who are at high risk for breast cancer be identified using bombesin estimation?

ABSTRACT Clinical follow-up studies of women with breast cystic disease indicate an increased risk of subsequent development of breast cancer, but the absolute risk marker has not yet been identified. It has been shown that bombesin/gastrin-releasing peptide can stimulate the proliferation of breast cancer cells in culture. In order to address the question of whether biological measurements might identify women with benign breast disease (BBD) at particular risk for breast cancer, analyses of bombesin and dehydroepiandrosterone sulfate (DHEAS) levels in tumor tissue from patients with breast cancer and BBD were carried out. The groups of patients comprised 13 women with breast cancer (mean age 52.3 years), 12 women with fibroadenoma (mean age 47.5 years), 6 with microcystic breast disease (mean age 43.5 years) and 6 with gross cystic breast disease (mean age 47.2 years). Malignant and benign tumor tissues were collected after mastectomy or tumorectomy. Bombesin and DHEA-S levels was measured by RIA after homogenization and extraction of tissues. Bombesin concentrations were higher in women with breast cancer (83.67±21.07 ng/g) than in other groups, except women with gross cystic disease (79.6±10.9 ng/g). In contrast, tissue concentrations of DHEAS in women with breast cancer (130.5±34.5 μg/g) were lower with comparison to the others, except women with fibroadenoma (177.7±84.9 μg/g). Bombesin and DHEAS tissue concentrations showed significant negative correlation only in women with fibroadenoma. All values are means±S.D. The significantly higher bombesin levels in tissues from women with breast cancer and in breast benign gross cystic disease (high risk of cancer) suggests the possible role of bombesin in the malignant process. Further studies are necessary to confirm these initial results.

A role of VLA-6 laminin receptor in invasion of breast carcinoma.

The integrin VLA-6 as a laminin receptor and laminin as a ligand for laminin receptor were detected immunohistochemically in normal, benign tumor and carcinoma tissues of the breast. Epithelial cells of both normal breast and benign tumor were in almost all cases strongly immunoreactive for VLA-6 in the plasma membrane. Carcinoma cells in 34 of 70 cases (49%) with an invasive component were not immunoreactive for VLA-6, and no carcinoma cells showed strong positivity. Although carcinoma cells in only four of 51 cases (8%) with intraductal components were negative for VLA-6, 37 cases (72%) showed weak expression of VLA-6 and 10 cases (20%) showed strong expression of VLA-6. A concordant expression of VLA-6 on carcinoma cells and laminin around carcinoma cell nests with an invasive component was observed, and VLA-6 expression in carcinoma cells was correlated to tubular formation in carcinoma cell nests as an indicator of differentiation. These findings suggest that loss of VLA-6 plays a role in the invasion of breast carcinoma, and that VLA-6 laminin receptor and laminin may contribute to tubular differentiation of breast carcinoma cells.

Loss of VLA‐2 Collagen Receptor in Breast Carcinoma, Facilitating Invasion and Metastasis

The integrin VLA‐2 as a collagen receptor and VLA‐5 as a fibronectin receptor were detected immunohistochemically in normal, benign tumor and carcinoma tissues of the breast. Both proteins were also detected by Western‐blot analysis in some carcinoma cases. Epithelial and myoepitheiial cells of both normal breast and benign tumor were in all cases immunoreactive for VLA‐2 in the plasma membrane. Carcinoma cells in the invasive component were not immunoreactive for VLA‐2 in 31 (46%) of 67 cases. Carcinoma cells in the intraductal components were negative for VLA‐2 in only 4 (11%) of 36 cases, while 20 cases (56%) showed weak expression and 12 cases (33%) showed strong expression. Metastatic carcinoma cells in the lymph nodes of 6 cases showed no immunoreactivity except in one case, whereas, again with the exception of one case, the carcinoma cells in the primary tumors did show VLA‐2 expression. With regard to VLA‐5, there was no difference in its expression in the invasive components and the intraductal components. These findings suggest that the loss of VLA‐2 plays a role in the invasion and metastasis of breast carcinoma.

Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells

Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M-PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.

Expression of α-Smooth Muscle Actin in Benign or Malignant Ovarian Tumors

We compared the expression of α-smooth muscle actin (α-SMA) between benign and malignant human ovarian tissues by immunohistochemical staining and Western blot analysis using the monoclonal antibody specific to α-SMA. In normal human ovaries, α-SMA was found in the blood vessels walls, muscle fibers, and stromal cells surrounding the follicles. The main source of α-SMA in the benign ovarian tumors was the blood vessel walls which highly expressed the α-SMA throughout the tumor. In malignant tumor tissues, however, the vessels located in or close to the cluster of cancer cells did not express α-SMA. It corresponded to the results of the Western blot analysis, showing that the amount of α-SMA in malignant ovarian tumor tissues was much smaller than that in benign tumor tissues. Thus, the alteration in α-SMA expression seems to reflect the qualitative difference in vessels between benign and malignant ovarian tissues, and therefore α-SMA is considered to potentially be a histopathologically useful marker for indicating the malignant potential of ovarian tumors.

Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumours of the central nervous system.

Point mutations in the transmembrane domain of c-erbB-2 gene in human brain tumours were studied by DNA amplification with the polymerase chain reaction method. Amplified gene fragments in M13 phage vector were cloned, and subsequent nucleotide sequences were determined. Studied specimens were 10 human malignant and 3 human benign tumours of the central nervous system, and a normal human placenta. In malignant tissues, Val-to-Glu mutation that induces transforming activity of c-erbB-2 did not appear to codon 659 of c-erbB-2. In malignant tissues, many other types of mutations appeared in low frequency, either at codon 659 or other positions of the transmembrane domain of c-erbB-2. The ratio of mutated genes to normal genes was very low in all specimens of malignant tumours. The point mutations were not observed in benign brain tumour or normal human placental tissues. The transmembrane domain of c-erbB-2 may have several highly mutable hot spots, where brain tumour tissues show a predilection for point mutation.

Peroxidase and coupling activities of thyroid peroxidase in benign and malignant thyroid tumor tissues.

The coupling activity of thyroid peroxidase (TPO) in thyroid glands from patients with benign adenoma, papillary carcinoma, and diffuse goiter (Graves' disease) was measured for the first time, in addition to the peroxidase activity of these tissues. The peroxidase activity of TPO in the mitochondria-microsomes fraction was measured with guaiacol or iodide as the second substrate. In the case of papillary carcinoma, the mean protein-based specific activity obtained by the guaiacol assay was about 1/7 of that of diffuse goiter. The iodide oxidation activity of carcinoma was very low, about 1/25 [corrected] of that in diffuse goiter and 1/70 of that in adenoma. The peroxidase activity in adenoma was almost similar in the guaiacol oxidation assay and approximately one half in the iodide oxidation assay as compared with that in diffuse goiter. There was a close correlation between the guaiacol and iodide oxidation assays in individual patients with adenoma and diffuse goiter, but not in patients with papillary carcinoma. The coupling activity of TPO was measured with thyroglobulin purified from pooled toxic diffuse goiters and chemically iodinated to contain little additional T3 and T4. The specific coupling activity of TPO in mitochondria-microsomes from carcinoma was significantly lower (about 1/5) than that of diffuse goiter, and the activity in adenoma was not significantly different (about 1/2) from that of diffuse goiter. The data of coupling activities has a close correlation with that of peroxidase activities in individual patients with adenoma but not in patients with carcinoma. Based on these findings, the qualitative abnormality of TPO and its relation to the cold 123I scintigram in thyroid tumors are discussed.

Epidermal growth factor receptors in intracranial and breast tumours: their clinical significance

A method to determine the binding of epidermal growth factor (EGF) to the particulate fraction of the cell has been established and evaluated using rat liver, human placenta, and tumours of human breast and brain. Little EGF receptor (EGFR) activity was detected in normal or benign tumour tissues except for meningioma (positive in 95% samples), but EGFR were present in 43% of 131 breast tumours and 75% of 55 primary cerebral tumours. Despite the strong inverse correlation between EGFR activity and oestrogen receptors in breast tumours and a tendency for high levels of EGFR activity to be associated with glioblastoma multiforme, analysis showed that EGFR was of little prognostic significance in patients with tumours of either breast or brain.

Inhibitory action of estradiol on growth promoting activity in extract from uterine cancers

Extracts from uterine cervical and body cancers, but not from benign tumor or intact tissues tested, were found to contain a growth-promoting activity which induced the proliferation of human endometrial fibroblasts. Exposure of cultured fibroblasts to the cancer extracts increased the rate of [3H]thymidine incorporation in a dose-dependent manner. The activity was heat-labile, and not inactivated by removal of lipid-soluble material suggesting that the activity is associated with a protein. When the fibroblasts were preincubated with estradiol for 12 hours, but not for 1 hour, the extract-induced fibroblast proliferation was suppressed. The inhibitory effect of estradiol was dose related (EC50: 10nM) and non-competitive, suggesting that the steroid may reduce the sensitivity of fibroblasts to the extracts. This is the first report to provide direct evidence that estradiol may play an inhibitory role in the action of growth factor-like peptide produced from malignant tumors.

The assessment of abnormal pelvic blood flow by transvaginal color and pulsed Doppler

Transvaginal color Doppler was used to analyze a group of 19 healthy, 48 infertile and 8 postmenopausal women; 67 patients with uterine and 151 patients with adnexal masses, and 19 patients with a suspected ectopic pregnancy. The ultrasonographer had not been informed of other clinical findings and indications for operative treatment. A 5 MHz transvaginal color Doppler probe was used to visualize the pelvic anatomy and blood flow. Each arterial blood flow velocity was classified into either of two types. In the normal flow pattern, the diastolic flow component was absent or small and the value of resistance index (RI) was greater than 0.50. In the abnormal flow pattern, a large diastolic flow component was evident and the value of RI was less than 0.50. Transvaginal color and pulsed Doppler studies in confirmed malignant uterine masses had moderate accuracy (90.2%), with a sensitivity (55.6%) and specificity (100%); and in confirmed malignant adnexal masses high accuracy (100%), sensitivity (100%) and specificity (100%). Comparison of blood flow characteristics within benign and malignant tumor tissue revealed less impedance and higher velocity in cases of malignancy. Blood flow studies in both uterine arterias have not shown clinically important values. This method can be also used in the diagnosis of ectopic pregnancy.

舌に発生したか粒細胞腫の１例

Granular cell tumor is a relatively rare soft tissue benign tumor. In this paper, a case report of the tumor occurring in the tongue of a 44-year-old man is presented. The histology was confirmed to that in Abrikossoff's classic description of the tumor. The patient was treated surgically and was well months later. Immunohistochemical and electron microscopic observations revealed that this tumor was strongly suggestive of peripheral nerve origin as reported by other investigators.

The gene for prolactin-inducible protein (PIP), uniquely expressed in exocrine organs, maps to chromosome 7.

The hormonally responsive prolactin-inducible protein (PIP) gene is expressed in benign and malignant breast tumor tissues and in such normal exocrine organs as sweat, salivary, and lacrimal glands. In this communication we report the regional chromosome localization of the PIP gene locus to chromosome 7 by Southern hybridization to DNA from human-hamster somatic cell hybrids, and to 7q32-36 by in situ hybridization.

ELEVATED LEVELS OF POLYAMINES AND THEIR DERIVATIVES IN BREAST CANCER TISSUES

Tissue polyamines were examined in 111 cases of breast cancer and 15 cases of benign breast tumor. Three common polyamines, i.e., putrescine, spermidine and spermine were found in all the tissue samples analyzed. The levels of the three polyamines were 5 to 7 times higher in breast cancer tissue than in normal breast tissue, and 2 to 4 times higher in cancer tissue than in benign breast tumors. Moreover, N1-acetylspermidine was detected in 89.2% of cancer tissue, 20.0% of benign tumor tissue and in only 2.0% of normal breast tissue.There was no significant difference in the polyamine levels of ER (estrogen receptor) -negative carcinomas and ER-positive carcinomas. The N1-Acetylspermidine levels of ER-negative tumors were higher than those of ER-positive tumors. Similar findings were found with respect to the PgR (Progesterone receptor) status of tumors. Putrescine levels of breast cancer tissue were significantly higher in pre-menopausal women than in the post-menopausal group. The spermidine levels of normal breast tissue were significantly higher in the pre-menopausal group than in the post-menopausal group.Besides the above three polyamines, two minor unknown polyamines, X-1 and X-2, were detected in about 9% of breast cancer tissue. The retention time of X-1 corresponded to that of homospermidine and the retention time of X-2 corresponded to that of aminopropylhomospermidine or canavalmine. The fraction containing X-1 was incubated with either putrescine oxidase or polyamine oxidase and the oxidation products were analyzed. Product analysis showed that X-1 was indeed identical to homospermidine.

Metabolism of estradiol by human breast cancer

The activities of estrogen- 2,4- and 16α-hydroxylase as well as 17β-hydroxysteroid dehydrogenase ( 17β-OHSDHase) were determined in normal, benign and mammary tumor breast tissues. All three hydroxylases were absent in both normal and benign tumor breast tissues. 17β-OHSDHase was absent from normal breast tissues but present in all benign tumor tissues. Estrogen- 2-hydroxylase was present in most breast carcinomas, was significantly higher in estrogen receptor (ER)-positive than ER-negative tumors, did not correlate with progesterone receptor (PR) and was significantly lower in the ER+PR− subgroup of breast cancers. 4-Hydroxylase activity did not correlate with either ER or PR content but was significantly lower in the ER+PR− subgroup of breast cancers. The activity of 16α-hydroxylase was present in only 18% of all tumors investigated ( 9 50 ), did not correlate with the ER or PR content and was completely absent in the ER+PR− and ER−PR+ subgroups. The activity of 17β-OHSDHase was significantly higher than the estrogen hydroxylase but did not correlate with either the ER or PR content, and was not different among the ERPR tumor subgroups. The physiological role of these enzymes in the metabolism of estradiol in relation to breast cancer is discussed.

Multielemental analysis of human thyroid glands using particle induced X-ray emission (PIXE)

PIXE spectroscopy has been applied to the analysis of human thyroid glands. Nontumor thyroid tissues taken from different patients showed almost the same composition which fell into the range of the data for normal thyroids given in the literature. On the other hand, a deficiency of iodine and iron was observed in all of the malignant and benign tumor tissues examined here. In some injured tissues considerable deviations of K and Ca from normal concentration levels were also recognized. This work demonstrates an important advantage of PIXE to analyze fugacious elements together with other elements simultaneously.

Malignant transformation of a benign cutaneous mixed tumour

Whilst benign cutaneous mixed tumour is common, malignant cutaneous mixed tumour is rare. There are only eleven accepted cases of the malignant counterpart in the literature. In none was there residual benign tumour tissue present to suggest that they arose from malignant transformation of the benign tumour. We report a very rare case of a malignant transformation of a benign cutaneous mixed tumour in an eighty-four year old female. Other unusual features in this case included considerable involvement of bone in the primary lesion and the histological picture of extreme pleomorphism and active mitoses, not seen in other reported cases of the malignant tumour.

Malignant Transformation of a Benign Cutaneous Mixed Tumour

Whilst benign cutaneous mixed tumour is common, malignant cutaneous mixed tumour is rare. There are only eleven accepted cases of the malignant counterpart in the literature. In none was there residual benign tumour tissue present to suggest that they arose from malignant transformation of the benign tumour. We report a very rare case of a malignant transformation of a benign cutaneous mixed tumour in an eighty-four year old female. Other unusual features in this case included considerable involvement of bone in the primary lesion and the histological picture of extreme pleomorphism and active mitoses, not seen in other reported cases of the malignant tumour.

Estrogen and progesterone receptors in human ovarian tumors

Estrogen and progesterone receptors were measured in cystosols prepared from 32 normal ovaries and 25 benign and 49 malignant ovarian tumors. In normal ovarian tissue, estrogen and progesterone receptors were detected in 22 and 75% of specimens, respectively. Estrogen receptors were present in low concentrations ranging from 2 to 9 fmol/mg cytosol protein. The estrogen receptor content and distribution were similar in benign tumors (20%), but progesterone receptors were significantly decreased in 16% of specimens ( P < 0.001). In malignant ovarian tissues, estrogen receptors were present in 57% of specimens in concentrations ranging from 1 to 132 fmol/mg cytosol protein. Of these, 72% of tissues had estrogen-receptor concentrations greater than 10 fmol/mg cytosol protein. The presence of estrogen receptors in ovarian cancer was significantly different from normal ovaries and benign tumor tissues ( P < 0.01). Progesterone receptors were detectable in 29% of ovarian cancer specimens. Estrogen and progesterone receptors were present alone or in combination, in 65% of ovarian cancers. The similarity in sex steroid content between ovarian and breast cancer warrants prospective studies of sex steroid receptor content in ovarian malignancies as a possible predictive index of survival and response to hormone therapy.

Total CK activity and isoenzyme patterns in normal and neoplastic tissue of gastrointestinal tract.

Total creatine kinase (CK) activity and isoenzyme distribution were determined in normal and tumour of gastrointestinal (GI) tract. Total CK activity per gram wet tissue appeared to be markedly reduced in malignant tumour tissue, yet it was raised in benign tumour tissue. CK-BB was the predominant isoenzyme in both normal and tumour tissue of GI tract. Alteration of isoenzyme pattern was noted between the normal and tumour tissue. In one patient, macro-CK was found in tissue homogenate.