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PubMed1997

Expression of the nm23 metastasis-suppressor gene product in skin tumors.

Nm23 is a gene with a putative metastasis-suppressor function, whose expression is inversely correlated with the metastatic potential of some solid malignancies. Because very few data exist concerning the role of nm23 in skin tumors, we studied the immunohistochemical expression of nm23 gene product in frozen sections of normal skin and of 104 cutaneous benign or malignant, epithelial and mesenchymal tumors. Nm23 was found expressed within basal cells of the epidermis and its appendages. All basal cell carcinomas showed diffuse immunoreactivity predominating within cells located at the periphery of tumor masses; in contrast, most squamous cell carcinomas, premalignant lesions and the benign epithelial lesions studied showed very weak, if any, immunoreactivity. Benign nevi and most malignant melanomas expressed nm23 immunoreactivity and the pattern observed was similar between primary and metastatic lesions. These results show that nm23 is differentially expressed in cutaneous tumors. It seems likely that the strong immunoreactivity of basal cell carcinomas, contrasting with the almost non-expression in squamous cell carcinomas, reflects the different metastatic potential of these two types of tumors. In melanomas, no direct correlation between the metastatic phenotype and nm23 expression could be detected. Our results suggest that the nm23 gene is involved in cutaneous carcinogenesis; its precise role deserves further study.

Antigens, Neoplasm↗

PubMed1997

Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response.

The patterns of differential gene expression were examined in two primary (A's) and two matched-metastatic (B's) head and neck squamous cell carcinoma (HNSCC) cell lines by differential display of mRNAs and northern blot hybridisation. Three cell lines used (PCI-04A, PCI-04B and PCI-06A) were established independently prior to therapy, whereas one cell line (PCI-06B) was established from a recurrent tumor after radiation therapy. A total of seven differentially displayed mRNA clones were identified, of which six clones were obtained by comparison of PCI-06A cells with PCI-06B cells (SCC-S1a/b, SCC-1c, and SCC-S2, PCI-06B; SCC-S3 to SCC-S5, PCI-06A), and one clone was obtained from the PCI-04A and PCI-04B match (SCC-Sa, PCI-04B). Based on the DNA database search for homology to the known sequences, six of the seven partial cDNA clones (SCC-S1a/b, SCC-1c, SCC-S2 to SCC-S4, and SCC-Sa may represent novel genes, whereas one cDNA clone (SCC-S5) shows significant homology to the HLA class II antigen gene (DPW2 beta chain). Each of the seven clones revealed preferential expression by northern blotting in the cell line of origin as compared to the matched counterpart. The transcripts ranged in size from approximately 7.0 Kb to 0.5 Kb. Interestingly, the SCC-Sa clone was preferentially expressed in both metastatic cell lines compared to the primary tumour-derived cell lines. We conclude that the SCC-Sa gene may be more commonly involved in tumour metastasis, whereas expression of the other genes (SCC-S1a/b, SCC-S1c, SCC-S2-SCC-S5) may be associated with metastasis and/or response of HNSCC to ionising radiation.

Base Sequence↗

PubMed1996

Presence of oncogenic HPV DNAs in cervical carcinoma tissues and pelvic lymph nodes associating with proliferating cell nuclear antigen expression.

The presence of oncogenic HPV DNAs (HPV-16/18) in cervical carcinomas and their normal and metastatic pelvic lymph nodes and the expression patterns of proliferating cell nuclear antigen (PCNA) in cervical carcinomas were retrospectively studied to elucidate the possible roles of them in malignant transformation and progression of the disease. HPV-16/18 DNAs were detected by polymerase chain reaction using HPV E6 type-specific primers in 79 patients with cervical cancer. 31 patients who had pelvic lymph node metastasis (group I) and 48 patients without pelvic lymph node metastasis (group II) who were proven by pathologic examination of surgical specimens. HPV-16 or -18 DNAs were detectable in cervical carcinoma tissues in 60 patients from 79 cervical cancer patients (75.9%; HPV-16 was 67.1% and HPV-18 was 8.9%). HPV DNAs were amplified from metastatic pelvic lymph nodes in 13 patients of group I (42%) and from nonmetastatic lymph nodes in 7 group I patients (22.5%). Recurrence was identified in 9 group I patients (29.0%) in 3 years of follow-up. HPV DNAs were amplified from nonmetastatic lymph nodes in 11 group II patients (22.9%). Two group II patients, who had HPV-16 DNA by PCR in nonmetastatic nodes, were recurrent. PCNA was overexpressed in 66.7% of HPV-16- or -18-positive cervical cancers and 16.7% of HPV-16- or -18-negative cervical cancers. However, the expression levels of PCNA in cervical cancers were not influenced by the presence of oncogenic HPV DNA or pathologic metastasis in the pelvic lymph nodes. In conclusion, HPV DNA could be amplified from some metastatic and nonmetastatic pelvic lymph nodes and the detectability of oncogenic HPV DNA in pelvic lymph nodes may represent the poor outcome in the treatment of disease. The expression of PCNA protein which was associated with presence of oncogenic HPV DNAs in cervical cancers, suggesting activation of S phase of cell cycle, may contribute to the malignant progression by HPV-16 or -18.

Base Sequence↗

PubMed1998

Power Doppler imaging of hepatic tumours: differential diagnosis between hepatocellular carcinoma and metastatic adenocarcinoma.

We evaluated the usefulness of power Doppler imaging in the differential diagnosis between hepatocellular carcinoma and metastatic adenocarcinoma. Forty-seven patients with hepatocellular carcinoma and 18 patients with metastatic adenocarcinoma were evaluated using power Doppler imaging. The colour signals of hepatic tumours were graded as follows: 1, colour signals only in the marginal area; 2, small dot or dotted line colour signals within the tumours; 3, continuous solid line colour signals within the tumours. The grade 3 colour signals were classified in the following three patterns; winding line pattern, stretched line pattern and mixed pattern. The colour signals of hepatocellular carcinoma were grade 1 in seven patients, grade 2 in 11 and grade 3 in 29. The colour signals of metastatic adenocarcinoma were grade 1 in three patients and grade 3 in 15. Of the 29 hepatocellular carcinoma patients with a grade 3 signal, 26 patients had winding line patterns and three had mixed patterns. Of the 15 metastatic adenocarcinoma patients with a grade 3 signal, 12 patients had stretched line patterns and three had mixed patterns. In conclusion, power Doppler imaging is useful in the differential diagnosis between hepatocellular carcinoma and metastatic adenocarcinoma to evaluate the colour signal pattern within the tumour.

Adenocarcinoma↗

PubMed1995

Modulation of tumor cell gene expression and phenotype by the organ-specific metastatic environment.

The mechanistic basis of a metastatic cell's ability to proliferate in the parenchyma of certain organs and develop organ-specific metastases is under intense investigation. Signals from paracrine or autocrine pathways, alone or in combination, may regulate tumor cell proliferation with the eventual outcome dependent on the net balance of stimulatory and inhibitory factors. This article summarizes recent reports from our laboratory and others demonstrating that the organ microenvironment can profoundly influence the pattern of gene expression and the biological phenotype of metastatic tumor cells, including induction of melanocyte stimulating hormone receptor and production of melanin, regulation of terminal differentiation and apoptosis, resistance to chemotherapy, and regulation of growth at the organ-specific metastatic site. These recent data from both murine and human tumor models support the concept that the microenvironment of different organs can influence the pattern of gene expression and hence the phenotype of tumor cells at different steps of the metastatic process. These findings have obvious implications for the therapy of neoplasms in general and metastases in particular.

Animals↗

PubMed1990

Patterns of failure in patients with stage I, grade 3 carcinoma of the endometrium.

Patients with high grade, early stage endometrial carcinoma are reported to have worse survival and local control rates than those with low grade carcinomas. To define failure patterns further in patients with FIGO Stage I, grade 3 endometrial carcinomas, the patients from three institutions who received adjuvant or definitive radiation (RT) were analyzed. Of 119 patients meeting the criteria of Stage I, grade 3 endometrial carcinoma, 57 patients received preoperative radiation, 49 patients received postoperative radiation, and 10 patients received definitive radiation with 5-year actuarial survival rates of 64%, 73%, and 65%, respectively. Three additional patients received both preoperative and postoperative treatment. The overall local control rate was 88% with a median follow-up of 70 months. Of 36 patients who failed, 14 had a component of local failure, and 31 had a component of distant failure. Eighteen of 31 distant failures involved metastatic spread to the abdominal cavity. Recurrence patterns by method of treatment are documented. Patients with high grade tumors do have a propensity for distant metastasis. Clinical investigation into the value of systemic therapy is necessary.

Adenocarcinoma↗

PubMed1985

Photic driving evoked by hemifield flickering dot pattern stimulation in a patient with brain tumor.

We have described photic driving evoked by hemifield 5/sec flickering dot pattern stimulation in a patient suffering from a metastatic tumor in the left parietal lobe. Based on an analysis of the photic driving in this particular patient, the left upper lip of the visual cortex is presumed to be the most sensitive to 5/sec flickering dot pattern stimulation. It is suggested that such an examination might be useful for determining local functional disturbance in the visual cortex.

Brain Neoplasms↗

PubMed1999

Infiltrative glomus tumor arising from a benign glomus tumor: a distinctive immunohistochemical pattern in the infiltrative component.

Malignant glomus tumors (MGT) are rare. Although metastatic MGT has been reported, most MGT have only been locally aggressive, some with multiple local recurrences. We report an additional case of an infiltrative glomus tumor. In addition to the pattern of immunohistochemical staining for alpha-smooth muscle actin (SM-actin) previously described, we performed immunohistochemical stains for Ki-67 and CD34. The infiltrative component of the glomus tumor showed variably decreased staining with SM-actin and occasional tumor cells showed nuclear staining with Ki-67. CD34 staining occurred in stromal cells forming the pseudocapsule in the benign component of this tumor and in other benign glomus tumors. The infiltrative component showed increased CD34 stromal cells. Although Ki-67 staining showed only an occasional proliferative cell, the immunohistochemical staining pattern of CD34 and SM-actin raise the possibility that the infiltrative component of this tumor may have differences in the degree of differentiation from the circumscribed part and that local factors could support its spread from a conventional benign glomus tumor.

Actins↗

PubMed1995

Changing pattern of expression of the epidermal growth factor receptor and transforming growth factor alpha in the progression of prostatic neoplasms.

The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were weakly positive in several cases. Malignant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-refractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metastases coexpressed the receptor and the ligand. These results suggest that, unlike primary prostate tumors where a paracrine relationship between EGFr and TGF-alpha appears to predominate, the potential for autocrine stimulation may exist in the majority of metastatic androgen-independent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androgen-independent condition suggests that strategies aimed at blocking this growth factor pathway may be of therapeutic importance for androgen-independent disease.

Adrenal Gland Neoplasms↗

PubMed1988

Fine-needle aspiration cytology of mesenchymal tumors of the breast.

This report describes the fine-needle aspiration (FNA) cytologic findings of 15 cases of sarcomas involving the breast out of a combined series of 2,064 breast FNA biopsies, including 580 malignancies, thereby accounting for 2.6% of all the malignant breast tumors. The series consisted of 14 women and one man with a mean age of 48.4 yr (range, 29-63). There were eight cases of cystosarcoma phyllodes, including one malignant cystosarcoma phyllodes. Three benign cystosarcoma phyllodes had a significant concomitant atypical epithelial hyperplasia, which lead to a misdiagnosis of carcinoma in two of the cases. The third case was correctly identified as recurrent cystosarcoma phyllodes. In retrospect, features suggestive for cystosarcoma phyllodes and unusual for breast carcinoma include increased numbers of naked nuclei and hypercellular stromal fragments. Sarcomatous patterns in our four metaplastic carcinomas included chondrosarcoma (two cases), malignant fibrous histiocytoma (MFH) (one case), and fibrosarcoma (one case). Two additional pure primary MFHs (both of which had electron microscopic confirmation) and one metastatic fibrosarcoma to the breast were encountered. Recognition of unusual cytologic patterns for breast carcinoma should suggest the possibility of a primary or metastatic sarcoma to the breast. Potential pitfalls for misdiagnosis include the presence of atypical epithelial hyperplasia in some cases of cystosarcoma phyllodes, along with occasional cases having patterns indistinguishable from a fibroadenoma. The pleomorphic and bizarre cellular features can suggest the diagnosis of metaplastic and pure sarcomas of the breast, although the potential exists for confusion with very poorly differentiated carcinoma. FNA diagnosis of sarcomatous lesions of the breast is essential in order to insure proper surgical treatment.

Adult↗

PubMedDate not supplied

[Doppler ultrasonography of superficial lymph nodes].

Normal lymph nodes (l.n.) are elongated and hypoechoic, with central echogenic hilum on B-mode, while color-doppler (CD) shows central hilar vascularization. Chronic inflammatory l.n. are elongated, with echogenic hilum, hilar vascularization on CD and resistance index (RI) 0.60-0.70. Acute lymphadenitis shows intensive hilar flow with RI<0.60; abscess of l.n. is anechoic with through transmission. Tuberculous l.n. are inhomogenously hypoechoic and rounded, with deformed hilar vascularization on CD, occasionally with centripetal flow. They may mimick malignant l.n. on CD due to vessel dislocation by granulomatous masses. L.n. in stage of micrometastasis are of similar structure as reactive l.n., with preserved hilar vascularization; as the metastasis grows, focal cortical expansion and/or destruction of intranodal structure with dislocation and compression of blood vessels may occur; vascular resistance is consecutively increased; in advanced stage of metastatic growth l.n. becomes rounded, hilum is not visible, cortex is heterogenous, occasionally with hyperechoic keratin deposits, unsharp nodal margin is the sign of extranodal neoplastic spread; mainly peripheral vascularization, with fragmentation, deformation and dislocation of intranodal vessels are seen on CD, with increased RI>0.80; necrotic areas are anechoic and avascular on CD. Lymphomatous nodes have preserved internal structure, sharp margins, hypoechoic cortex, frequently with through transmission; large arborized hilum may be displaced; abundant hilar flow is seen on CD, with normal or slightly increased vascular resistance. Although the sensitivity of B-mode and Doppler features of l.n. is mostly limited (false negative rate is significant), high specificity of some of them establishes sonography as a valuable complementary method in differential diagnosis of lymphadenopathy: the presence of hilar vascularization with RI<0.40 accurately indicates acute lymphadenitis, while predominantly peripheral flow pattern and RI>0.80 are typical of metastatic l.n. High enddiastolic velocities (EDV>9 cm/s) are only rarely seen in metastases, while very low EDV<1 cm/s indicates metastatic lymphadenopathy. As sonography is very suitable imaging method for puncture guidance, B-mode and CD analysis of l.n. need to be combined with aspiration cytology whenever possible, as it may considerably improve the accuracy of non-invasive patient diagnostic work-up. Literature on sonography of l.n. was reviewed, and selection of most relevant articles was made.

Humans↗

PubMed2001

Microcirculation patterns other than loops and networks in choroidal and ciliary body melanomas.

PURPOSE: To provide ophthalmologists and pathologists with expanded criteria for separating patients at high risk of metastatic melanoma from those at low risk on the basis of microcirculation patterns in choroidal and ciliary body melanomas. DESIGN: Tissue culture studies and observational case series. PARTICIPANTS: The pattern-forming ability of four uveal melanoma cell lines of varying degrees of aggressive behavior was studied in vitro. Histologic sections of 234 eyes removed for choroidal or ciliary body melanoma were studied for the presence of microcirculation patterns. METHODS: The study was divided into two phases: the study of histologic sections of eyes removed for choroidal and ciliary body melanomas and observations on the in vitro behavior of cultured melanoma cells of varying degrees of invasive behavior. The presence or absence of each of nine microcirculation patterns was recorded from tissue sections, and interrelationships between different patterns were explored statistically. In vitro reconstitution of patterns and a study of the interrelationships of patterns in histologic sections was carried out. In the in vitro studies, uveal melanoma cell lines of varying degrees of aggressive potential were cultured to observe the development of architectural patterns other than loops and networks. MAIN OUTCOME MEASURES: In histologic studies, the outcome measure was the conditional probability of detecting loops or networks given the presence or absence of other patterns positive for periodic acid-SCHIFF: For tissue culture studies, the outcome measure was either the development or lack of development of patterns of different shapes in vitro. RESULTS: Histologic studies disclosed that given the presence of arcs without or with branching in a tissue section, it is likely that loops or networks will be detected in the same section plane, suggesting that the production of these patterns by aggressive tumor cells reflects a spectrum of architectural potential. In vitro studies confirmed this hypothesis by revealing that highly aggressive and metastatic uveal melanoma cell lines, but not poorly aggressive tumor cell lines, generated parallel channels with and without crosslinking and arcs with and without branching as well as loops and networks. CONCLUSIONS: The criteria for separating patients into low- and high-risk categories for metastasis from uveal melanoma should be expanded to include patterns other than loops or networks. In both the pathology laboratory as well as in a clinical setting, the detection of arcs or arcs with branching and parallel channels should prompt a careful search for loops and networks and for crosslinking parallel channels, respectively.

Choroid Neoplasms↗

PubMed2000

Malignant cell detection by fluorescence in situ hybridization (FISH) in effusions from patients with carcinoma.

Cytological diagnosis of malignant cells in effusions is hampered by difficulties in the differentiation from reactive mesothelial cells. Because interphase cytogenetics by fluorescence in situ hybridization (FISH) might complement cytological evaluation, we determined the power of tumor cell detection using FISH and cytology in 201 effusions from patients with advanced cancer. Furthermore, 9 primary breast tumors were FISH-karyotyped, and chromosomal aberrations were compared with those of corresponding metastatic effusion cells. By using centromeric probes representing chromosomes 7, 8, 11, 12, 17, and 18, a rate of malignancy-associated aneusomy combined for the 6 chromosomes was detected in an overall of 44.8% of effusion specimens (range, 31.8% to 39.3% for the individual chromosome), comparable to cytology (43.3%). The combination of just 2 FISH probes (namely, representing chromosome pairs 8/11 and 8/17) was almost equally efficient in the identification of aneusomy. Approximately one fourth of the cytologically negative effusions were FISH positive and vice versa. From the initially FISH-negative effusions, 18.9% could be subsequently classified positive with dual-color FISH by visualization of intranuclear chromosomal complexity in rare aneuploid cells. Thus, "overall FISH analysis," including dual-color evaluation, identified tumor cells in significantly more effusions (55.2%, P = .001) than conventional cytology, implying greater sensitivity. Finally, our finding that numerical aberration patterns in primary breast tumors and corresponding metastatic effusions are comparable indicates that FISH examination of primary tumors will indicate the centromeric probe(s) best suited for an efficient search for metastasis in the individual case.

Adenocarcinoma↗

PubMed1994

Microcirculation architecture of melanocytic nevi and malignant melanomas of the ciliary body and choroid. A comparative histopathologic and ultrastructural study.

PURPOSE: This study was designed to (1) describe the vascular patterns of ciliary body and choroidal nevi by light microscopy, (2) compare the vascular ultrastructure of nevi with vessels of the normal uvea and uveal melanomas, and (3) compare the behavior of ciliochoroidal melanomas with and without a nevus-like vascular architecture. METHODS: After delineating the vascular patterns of 23 choroidal and ciliary body nevi by light microscopy, the authors identified 49 melanomas that had the same vascular patterns as nevi from a previously published series of 234 uveal melanomas. The survival of these 49 patients who had melanomas with a nevus-like vascular architecture was compared with the 185 patients who had melanomas that lacked this vascular profile. RESULTS: By light microscopy, the only vascular patterns identified in nevi are "normal" vessels, zones of avascularity ("silent" pattern), straight, and parallel vessels; closed vascular loops and networks were not detected in nevi. By transmission electron microscopy, the vascular basement membrane of malignant melanomas was multilaminar, fragmented, and significantly thicker than in normal eyes or nevi. None of the patients with nevi died of metastatic disease. Fourteen percent of patients whose melanomas had the same vascular profile as nevi died of metastatic disease, whereas 32% of patients whose melanomas had vascular patterns other than those seen in nevi died of metastatic melanoma (P = 0.012). CONCLUSIONS: The microcirculation architecture marks tumor progression in uveal melanocytic lesions by light and electron microscopy. In the spectrum of these lesions, nevi are benign, melanomas that have the same vascular profile as nevi have an intermediate biologic behavior, and melanomas with vascular networks are strongly associated with death due to metastatic disease.

Adolescent↗

PubMed1991

Role of the transitional mucosa of the colon in differentiating primary adenocarcinoma from carcinomas metastatic to the colon. An immunohistochemical study.

Differentiation between primary colonic adenocarcinoma arising in flat mucosa and carcinoma metastatic to the colon is often difficult. Examination of the mucosa adjacent to the tumor, the so-called transitional mucosa (TM), may be helpful. The morphologic, ultrastructural, and histochemical characteristics of the TM have been reported previously in detail. In this study the morphologic and immunohistochemical characteristics of the TM have been compared in 18 cases of primary colonic adenocarcinoma and 13 cases of metastasis to the colon. Five immunophenotypic markers were used: carcinoembryonic antigen (CEA), Lewis (x) and (y) blood group antigens, ras oncogene p21, and tumor-associated glycoprotein (TAG-72). Neoplastic transformation of colonic epithelium is associated with altered expression of these antigens. The morphologic and immunohistochemical profile of the TM was similar in both primary colonic adenocarcinomas and metastases to the colon. In some cases the TM adjacent to colonic metastases stained with one or more antibodies while the metastatic tumor was negative. Therefore, in cases where differentiation between primary colonic adenocarcinoma arising in flat mucosa and metastasis is difficult, the use of these reagents, particularly CEA, TAG-72, or ras oncogene p21, may be helpful. The similar immunohistochemical staining pattern of the TM in both primary and metastatic colon lesions supports a reactive, non-neoplastic origin of the TM. Furthermore, expression of these antigens is not limited to neoplastic epithelial cells.

Adenocarcinoma↗

PubMedDate not supplied

Metastatic phenotype: growth factor dependence and integrin expression.

Homogeneous subpopulations, which are endowed with low or high metastatic potential, were selected from Lewis lung carcinoma (3LL) in an attempt to correlate metastatic phenotype with specific properties of tumor cells. Since the growth of malignant cells at secondary sites could depend on their ability to respond to microenvironments, the growth factor dependence of 3LL variants has been studied. The ability of variant lines to grow in monolayer and in soft agar cultures, either in the presence or absence of different growth factors or serum, was analyzed and correlated with their metastatic potential. The reported results demonstrate that tumor cells expressing higher metastatic potential also exhibit higher capacity to grow and proliferate in all the culture conditions tested, independently of the addition of exogenous growth factors or serum. Moreover, since highly metastasizing cells express a significant amount of TGF-beta 1 mRNA, a pattern of autocrine growth is postulated for 3LL metastatic cells. One relevant aspect of the phenotype of transformed cells is their reduced adhesion to solid substrates; this phenomenon is thought to reflect the invasive and metastatic potential of tumor cells. Since the adhesion of the cells to substrata is mediated by molecules of the extracellular matrix, the expression of extracellular matrix receptors (integrins) was studied on 3LL metastatic variants. In particular, through immunochemical and biochemical studies we investigated the expression of the laminin receptor(alpha 6/beta 1) and of a novel receptor (integrin: alpha 6/beta 4), of unknown function. The receptors were quantitated on the cell surface of 3LL variants by the use of specific monoclonal antibodies which recognize, respectively, different epitopes of alpha 6, beta 4 or beta 1 subunits. Results demonstrate that the novel integrin alpha 6/beta 4, is specifically expressed in highly metastasizing 3LL cells, whereas the laminin receptor alpha 6/beta 1 is expressed in all 3LL variants. In conclusion, data presented demonstrate that 3LL cells endowed with higher metastatic potential are more independent of the microenvironmental conditions in that they possess a higher autocrine capacity than the lower metastasizing ones, and could acquire higher capacity to invade through the expression on their cell surface of specific receptors for cell adhesion (the novel integrin, defined as alpha 6/beta 4).

Animals↗

PubMed2003

Breast cancer patients with bone metastases are characterised by increased levels of nonisomerised type I collagen fragments.

BACKGROUND: Fragments of collagen type I containing the epitope AHDGGR (CTX) are generated during bone resorption. The aspartyl-glycine (DG) site within CTX is synthesised in the L-aspartyl peptide (alphaL) form, but converts to the age-modified forms L-isoaspartyl peptide (betaL) and D-aspartyl peptide (alphaD) over time. The purpose of the present study was to test the ability of the various CTX forms to identify breast cancer patients with bone metastases and to investigate whether such patients had an altered CTX excretion pattern. METHODS: In this cross-sectional study we compared CTX excretion in healthy premenopausal and postmenopausal women with CTX levels in patients with breast cancer. The breast cancer cohort comprised eight hypercalcemic patients with bone metastases (HC+), 100 normocalcemic patients with bone metastases (NC+) and 15 normocalcemic patients without bone metastases (NC-). RESULTS: In HC+ patients and NC+ patients, the excretion of alphaL CTX was highly increased compared with NC- patients (P < 0.01), with Z scores of 3.4 and 2.0, respectively. The excretion of the age-modified forms (betaL and alphaD CTX) was less increased in HC+ patients and in NC+ patients as compared with NC- patients, with Z scores of 2.2 and 1.0, respectively, for betaL CTX, and of 1.6 and 0.8, respectively, for alphaD CTX. CONCLUSION: Assays for the various isoforms of CTX have different sensitivities to identify patients affected by bone metastases. The alphaL CTX isoform reflecting resorption of young bone appeared to provide the best differentiation of patients affected by breast cancer-induced bone metastases. In conclusion, patients affected by metastatic bone disease present an altered excretion pattern of CTX isoforms.

Adult↗

PubMed1994

Role of DNA ploidy patterns in esophageal squamous cell carcinoma. An ultraviolet microspectrophotometric study.

BACKGROUND: Controversy still exists about the influence of DNA content on the prognosis for patients with esophageal squamous cell carcinoma. METHODS: DNA ploidy was determined by microspectrophotometric (MSPM) analysis of paraffin embedded malignant tissue from 78 patients with squamous cell carcinoma of the esophagus. The DNA distribution pattern was classified as diploid, low grade aneuploid (LGA), and high grade aneuploid (HGA) pattern. The relationships among DNA distribution patterns, pathologic features, clinical findings, and prognoses were investigated. Twenty-seven of 78 patients were also selected for analyses of the DNA ploidy pattern of lymph node metastases. RESULTS: Of 78 cancers, 20 (26%) were diploid, 15 (19%) LGA, and 43 (55%) HGA. The advanced carcinomas had the higher distribution of HGA pattern (55%), whereas the diploid pattern was more frequent in early stage (70%) or superficial (65%) esophageal cancer. In patients with the HGA pattern, there was a significantly higher frequency of lymph node metastases (79%) and marked lymphatic (74.4%) and vascular (69.8%) invasion compared with those exhibiting the LGA (33.3%) or diploid (25%) pattern. Five-year survival rates for patients with diploid carcinoma (57%) was significantly better than for those with the HGA pattern (14%). The distribution of nuclear DNA content was much narrower in the metastatic lymph node than in the corresponding primary cases. CONCLUSIONS: The HGA of DNA pattern based on spectrophotometry closely correlated with the factors generally indicative of the aggressive behavior of malignant tumors. Therefore, the role of the DNA ploidy pattern as a prognostic factor was emphasized.

Aged↗