Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone sialoprotein (BSP) and osteopontin (OPN) are prominent, mineral-associated proteins in the extracellular matrix of bone that have been implicated in the metastatic activity of cancer cells. The expression of BSP, which is normally restricted to mineralizing tissues, has been observed in cancers with a high propensity for forming bone metastases. To investigate the relationship between BSP expression and the formation of bone metastases we have conducted an initial study of the expression of BSP in 10 intraductal breast carcinoma bone metastases using immunostaining and in situ hybridization, and compared the expression with OPN. The metastases were characterized by the infiltration of tumour cells into bone with extensive bone resorption evident. Moderate to strong staining for BSP was observed in all (100%) carcinomas, which also expressed BSP mRNA as determined by in situ hybridization. Variable staining for BSP was also observed in the mineralized bone and expression of BSP mRNA could be observed in osteoblastic cells on the bone surface and in some osteocytes at sites of bone remodelling. Contrary to a previous report, BSP expression could be demonstrated by PCR in three breast cancer cell lines, MCF-7, T47-D and MDA-MB-231. Moreover, in sub-cutaneous tumours formed by MDA-MB-231 breast cancer cells injected into athymic mice, higher immunostaining for BSP was seen in large ulcerating tumours in which mineral deposits were formed. In contrast to BSP, staining for OPN in bone metastases was generally restricted to the interface between tumor cells and bone surface of the carcinomas. While OPN staining was also observed in the cytoplasm of osteoclasts, which showed strong hybridization to a digoxygenin-labelled OPN cRNA probe, expression of OPN was not clearly detectable in the tumour cells. These studies provide the first demonstration of BSP expression by tumour cells in bone metastases and support the concept that BSP may have a role in targeting metastatic cells to bone. Expression of OPN in bone metastases appears to be related to increased bone resorptive activity by osteoclasts.
Clin Exp Metastasis 2000
PMID:Expression of bone sialoprotein and osteopontin in breast cancer bone metastases. 1131 99

A small percentage of breast cancers are not visible on mammography. Since mammographically occult malignancies may be more difficult to diagnose, we hypothesized that the lack of visualization would cause a delay in detection, more aggressive surgical and adjuvant therapy, and poorer outcome. Patients with mammographically occult malignancies were compared to patients with cancers visible on mammogram. The significance of mammographic visibility for treatment and local and distant recurrence rates were evaluated. Ninety-one of the 813 (11%) cancers were mammographically occult. Patients with mammographically occult malignancies were significantly younger, of lower body weight, and had fewer pregnancies than patients with cancers visible on mammography: age, body weight, and parity were statistically significant (p < 0.001) in stepwise logistic regression. Ductal carcinoma in situ was significantly more frequently diagnosed in patients with mammographically visible malignancies (14% versus 4%, p = 0.0163) and nodal involvement was significantly more frequent in patients with mammographically occult malignancies (35% versus 24%, p = 0.0391). Diagnostic delays exceeding 3 months were experienced by 24% of patients with mammographically occult malignancies compared to 13% of patients with tumor visible on mammography (p < 0.0001). Adjuvant chemotherapy was given to 63% of patients with occult malignancies compared to 41% of patients with mammographically visible cancers (p = 0.0027). The use of breast-conserving therapy and adjuvant radiation and tamoxifen were comparable. Survival free of local recurrence and distant metastases for the 403 patients followed for 5 years or more was not related to mammographic visibility.
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PMID:Mammographically Occult Breast Cancers. 1134 51

Occult primary breast carcinoma presenting as isolated ipsilateral axillary lymph node metastases in patients with normal mammograms and normal physical exams accounts for less than 1% of all breast carcinomas. Contrast-enhanced magnetic resonance imaging (MRI) may identify the site of primary breast carcinoma and effect management of these patients. We report on eight consecutive women evaluated in our multidisciplinary clinic who had biopsy-proven metastatic adenocarcinomas to axillary lymph nodes and occult primary carcinomas. Each patient underwent MRI at 1.5 T with a volumetric fast-spoiled gradient-echo (3D FSPGR) pulse sequence before and after injection of gadopentetate dimeglumine. Wire localization of suspicious areas of enhancement was performed under MRI or mammography guidance followed by surgical excision. Seven (88%) of the eight normal mammograms showed dense (>50%) breast parenchyma. In two (25%) of the eight patients, suspicious focal or regional enhancement was seen on MRI. Following wire localization and excision, pathologic exam showed an invasive ductal carcinoma and ductal carcinoma in situ with invasion corresponding to the MRI enhancement in the two cases. Breast MRI can identify the primary tumor site and influence management of patients presenting with clinically and mammographically occult primary breast carcinomas.
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PMID:Breast MRI in the Evaluation of Patients with Occult Primary Breast Carcinoma. 1134 92

Axillary lymph node status continues to be the single most important prognostic variable for breast cancer survival despite significant progress in the molecular and genetic characterization of breast malignancies. All patients with invasive breast cancer who underwent axillary lymph node dissection as part of their treatment were evaluated by 11 clinical and pathologic factors, including the primary lesion's T category (TNM staging system), whether the lesion was clinically palpable, the presence of lymphatic or vascular invasion, nuclear grade, estrogen and progesterone receptors, S-phase, age, HER2/neu overexpression, histology (infiltrating lobular or ductal), and ploidy. A total of 2282 axillary dissections were performed: 391 in patients with ductal carcinoma in situ (DCIS) [3 of which (0.8%) contained metastases] and 1891 in patients with invasive breast cancer [680 of which (36%) contained metastases]. Multivariate analysis of patients with invasive cancer identified four factors as independent predictors of axillary lymph node metastases: lymph/vascular invasion, tumor size, nuclear grade, tumor palpability. Among a group of 189 patients with nonpalpable, non-high-grade invasive lesions 15 mm or smaller without lymph/vascular invasion, only 6 (3%) had metastases to lymph nodes. If any three of the favorable factors were present, lymph node positivity was 6% or less. Clinical and pathologic feature of the primary lesions can be used to estimate the risk of axillary lymph node metastases. Such risk assessment can be used for the treatment decision-making process.
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PMID:Predicting axillary nodal positivity in 2282 patients with breast carcinoma. 1137 14

CD31, an adhesion molecule expressed by endothelial cells, leukocytes, and platelets, is used in surgical pathology as a marker of normal and neoplastic vascularization. During the assessment of angiogenesis in breast carcinomas, CD31 expression was observed in a single case of large (5.2 cm diameter) high nuclear grade ductal carcinoma in situ (HG-DCIS) associated with poorly differentiated invasive ductal carcinoma (G3-IDC). Expression was limited to the cell membrane. This study focused on 32 HG-DCIS> or = 2 cm, either pure or associated with IDC. Cancer cells wereCD31(+) in 11 cases. Double staining using anti-CD31 monoclonal antibody (MAb) and anti-CD44 MAb, the anti-hyaluronate receptor, showed that foci of CD31(+) and CD44(-) tumour cells could be traced throughout the glandular tree, marking the intraductal diffusion of tumour up to Paget's cells at the nipple. The associated G3-IDC and their lymph node metastases were instead CD31(+) and CD44(+). CD31(+) tumours were oestrogen receptor (ER)(-), frequently p53(+) and c-erb-B2(+), and infiltrated by CD4(+) T lymphocytes. Normal and hyperplastic epithelia were constantly CD31(-). Other endothelial markers (e.g Factor VIII-RA and CD34) were not expressed by carcinoma cells, as was CD38, the CD31 ligand. In conclusion, CD31 expression is a feature acquired by breast cancer cells in the DCIS model. CD31 expression mainly correlates with tumour cells spreading within the ductal system. Finally, the invasive phenotype requires the co-expression of CD31 and CD44.
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PMID:Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast. 1185 2

Fasting blood samples were obtained before definitive surgery or biopsy in 128 patients referred to the department of surgery with suspected or manifest breast cancer. Insulin-like growth factor (IGF)-I, IGF-II and free IGF-I were measured by radioimmunoassay/immunoradiometric assay, while IGFBP-3 proteolysis was evaluated by Western immunoblot. 12 patients had ductal carcinoma in situ benign conditions, while staging revealed metastatic disease in 15 of 16 patients with invasive cancers. IGFBP-3 proteolysis above the normal range was recorded in 19 patients with invasive cancers, but in none of the patients suffering from DCIS/benign conditions. Increased IGFBP-3 proteolysis was most frequently recorded in patients harbouring large tumours and metastatic disease (Stage I: 0/19, 0%; Stage II: 3/45, 7%, Stage III: 9/37, 24%, and Stage IV: 7/15, 47%). IGFBP-3 proteolysis was significantly higher in Stage III (P =0.01) and IV (P< 0.001) patients compared to the other stage groups (P = 0.001). IGF-I and IGF-II correlated negatively to IGFBP-3 proteolysis and age. Plasma levels of IGF-I and -II were significantly lower in patients with elevated IGFBP-3 proteolysis compared to those within the normal range. Our findings reveal alterations in the IGF-system among a substantial number of patients with large primary breast cancers.
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PMID:Plasma insulin-like growth factor binding protein-3 proteolysis is increased in primary breast cancer. 1143 5

Amplification of int-2/FGF-3 gene was investigated by differential polymerase chain reaction (dPCR) in 440 archival primary breast carcinoma tissues. Of these, 23 were comedo ductal carcinoma in situ (DCIS), 18 were non-comedo DCIS, 41 were comedo DCIS with adjacent invasive ductal carcinomas, 19 were non-comedo DCIS with adjacent invasive ductal carcinomas, 270 were invasive ductal carcinomas, 33 were invasive lobular carcinomas, 21 were colloid carcinomas and 15 were medullary carcinomas. Int-2 was amplified in 22% (96/440) of the primary breast carcinomas. It was shown that int-2 was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 29% (12/41) of the adjacent invasive ductal carcinomas, 26% (71/270) of the invasive ductal carcinomas, 18% (6/33) of the invasive lobular carcinomas, 10% (2/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. In contrast, int-2 was not amplified in non-comedo DCIS and invasive ductal carcinomas with adjacent non-comedo DCIS lesions. A significant association was observed between int-2 amplification in the in situ components and adjacent invasive lesion (P<0.05). All tumors with int-2 amplification in the in situ lesions (7/7) also demonstrated same degree of amplification in the adjacent invasive components. However, 9% (5/53) of the tumors with no amplified int-2 gene in the in situ components showed int-2 amplification in the adjacent invasive lesions. A significant relationship was noted between amplification of int-2 and lymph node metastases (P<0.05) and poorly differentiated tumors (P<0.05) but not with estrogen receptor status (P>0.05) and proliferation index (Ki-67 and PCNA) (P>0.05). In Malaysia, majority of the patients belong to younger age group (<50 years old) but a comparison of the age groups showed that the amplification of int-2 was not statistically associated with patient age (P>0.05). These observations indicate that amplification of int-2 tends to strengthen the view that int-2 may have the potential to be an indicator of poor prognosis regardless of the age of the patient. Moreover, the presence of int-2 amplification in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that int-2 could be a marker of genetic instability occurring in early and late stages of tumor development.
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PMID:Detection of amplified int-2/FGF-3 gene in primary breast carcinomas using differential polymerase chain reaction. 1144 74

Myoepithelial cells (MCs) constitute the basal cell layer of normal mammary epithelia, and their identification is of particular diagnostic value because they are retained in most benign lesions while being lost in malignancy. Several MC immunocytochemical markers are currently available for diagnostic purposes, with special reference to smooth muscle-related antigens. p63 is a member of the p53 gene family, and its germline mutations are associated with severe mammary developmental defects in both rodents and humans. Different p63 isoforms have been identified, some of which (DeltaNp63) are preferentially expressed in the epithelial basal cells of different organs and have been considered as possible markers of stem cells/reserve cells. We investigated immunohistochemically 384 samples of normal and diseased human breast, including 300 invasive carcinomas, using four antibodies recognizing all p63 isoforms, or the DeltaNp63 isoforms. Twenty cytologic specimens were also investigated. Furthermore, snap-frozen tissue samples from three fibroadenomas and 10 invasive ductal carcinomas with their paired non-neoplastic tissues and three corresponding lymph node metastases were evaluated for the expression of p63 mRNA by RT-PCR. In normal breast tissue p63 immunoreactivity was confined to the nuclei of MCs. In all benign lesions p63-immunoreactive cells formed a continuous basal rim along the epithelial structures. Stromal cells, and in particular myofibroblasts, were consistently unreactive. Adenomyoepitheliomas showed nuclear staining in most neoplastic cells. A peripheral rim of p63-immunoreactive cells was retained surrounding lobular and ductal carcinoma in situ, although it was discontinuous as opposed to the normal structures. Invasive breast carcinomas were consistently devoid of nuclear p63 staining, with the exception of the two adenoid-cystic carcinomas, of the two ductal carcinomas with squamous metaplasia, and of 11 (4.6%) ductal carcinomas not otherwise specified, showing p63 immunoreactivity in a minor fraction (5-15%) of the neoplastic cells. In comparison with other MC markers, p63 was the most specific, being restricted exclusively to MCs, whereas antibodies to smooth muscle actin and, to a lesser extent, calponin also decorated stromal myofibroblasts. In the cytologic preparations p63 immunoreactivity was a consistent feature of "naked nuclei" and of a subset of cells surrounding benign epithelial clusters. RT-PCR experiments with primers specific for different p63 isoforms documented that normal tissues and fibroadenomas preferentially expressed the DeltaNp63 isoforms. Our study demonstrates that in normal and pathologic breast tissues MCs consistently express the DeltaNp63 isoforms. We suggest p63 as a reliable, highly specific, and sensitive MC marker in both histologic and cytologic preparations. Furthermore, because p63 immunoreactivity in adult epithelia is normally restricted to progenitor cells, it can be speculated that it might be a clue for the identification of the still elusive breast progenitor cells.
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PMID:p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. 1147 90

The purpose of this study was to evaluate and compare the diagnostic accuracy of pentavalent technetium-99m dimercaptosuccinic acid [99mTc-(V)DMSA] and 99mTc-methoxyisobutylisonitrile (MIBI) in the detection of primary breast cancer and metastatic lymph node involvement, and in the clarification of cases with indeterminate mammograms. Forty-one women (mean age+/-SD 55+/-7 years) referred for a suspicious breast lesion on physical examination and/or an abnormal mammogram underwent MIBI and (V)DMSA scintimammography (SMM) at separate sessions (48-h interval). Lateral prone and anterior supine images were obtained at 10 and 60 min after administration of 740-925 MBq of each tracer, in the arm contralateral to the breast lesion. The ipsilateral axillary region was also included in the field of view. The results of SMM and mammography were compared with histological findings. Breast cancer was histologically confirmed in 26 patients (mean diameter+/-SD 2.87+/-1.5 cm). Benign lesions were found in 15 patients (mean diameter+/-SD 2.04+/-2.7 cm). Mammography was definitely positive in 23/26 patients with breast cancer and indeterminate in 3/26 (sensitivity 88.4%). In benign lesions, mammography was true negative in 5/15 cases and indeterminate in 10/15 (specificity 33.3%). Both MIBI and (V)DMSA SMM detected 23/26 breast cancers (sensitivity 88.4%) and were true negative in 14/15 (specificity 93.3%). T/B ratios for breast cancer in MIBI and (V)DMSA scans were similar, and significantly higher than for benign lesions. MIBI correctly diagnosed 12/13 and (V)DMSA 11/13 cases in which the findings of mammography were indeterminate. In addition, (V)DMSA detected seven of eight cases of in situ ductal carcinoma (DCIS) associated with infiltrating carcinomas, while MIBI detected only two of these eight cases. (V)DSMA was also diffusely concentrated in benign lesions complicated by epithelial hyperplasia. Metastatic lymph node involvement was successfully imaged in 15/19 patients with metastatic disease by both agents (sensitivity 78.9%), while true-negative scans were observed in 19/22 (specificity 86.3%) patients with benign or malignant tumours without lymph node metastases. Linear regression analysis revealed a high coefficient of correlation between the (V)DMSA and the MIBI T/B ratios (r=0.8 P<0.001). We conclude that both (V)DMSA and MIBI show an excellent ability to detect breast cancer and its lymph node metastases. (V)DMSA also has a tendency to be diffusely and more intensely localised than MIBI in pre-invasive lesions, such as DCIS or epitheliosis, which are at risk of developing into malignancies. (V)DMSA could therefore provide a useful tool in the diagnosis of such lesions and possibly modify a predefined surgical plan. Finally, we believe that both tracers could offer an alternative method for elucidating nondiagnostic mammograms.
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PMID:99mTc-(V)DMSA scintimammography in the assessment of breast lesions: comparative study with 99mTc-MIBI. 1150 92

We review recent reports on breast cancer and its predictors, emphasizing the clinical utility of tissue samples from patients. We highlight indicators of increased cancer risk and lesions without metastatic capacity at time of detection, but of sufficient risk of attaining metastatic capacity that treatment is mandated ( ie, ductal carcinoma in situ ). Emphasized are histologic features of importance in stratification of ductal carcinoma in situ. We also review invasive lesions with little capacity for metastatic behavior and indicators of low malignant potential. Included are several papers reviewing the usefulness of histologic grading, emphasizing mitotic counts. Also, the continuing utility of recognizing some special and unusual types of breast cancer is detailed. Sentinel lymph node evaluation by histology is included because some minimal or artifactual findings in lymph nodes can mimic true metastases.
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PMID:Pathology of preinvasive and excellent prognosis breast cancer. 1167 81


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