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PubMed2001

Prognostic impact of tumor perfusion in MR-imaging studies in Ewing tumors.

BACKGROUND: Intratumoral hypoxia is associated with poor prognosis in various solid tumors. Severe and long-lasting hypoxia results in necrosis. The presence of necrosis therefore might also be correlated with unfavorable outcome. This has been demonstrated for head and neck cancers, gliomas and adult soft tissue sarcomas. We have investigated whether or not the patterns of contrast enhancement and the presence of visible necrosis on pretreatment MR images has prognostic impact in Ewing tumors. PATIENTS AND METHODS: From December 1993 though March 1997, 79 patients with Ewing tumors were prospectively analyzed for the presence and amount of necrosis in their tumors. The median age was 12 years (range 4-30 years). The median follow-up at the time of this analyses was 3 years. All patients were treated according to the multicentric EICESS-92 protocol with multi-agent chemotherapy (VACA or VAIA or EVAIA) and local therapy (radiotherapy with 50-60 Gy or surgery or surgery with pre- or postoperative irradiation with 45-50 Gy). For the measurement of necrosis, gadolinium contrast-enhanced T1-weighted MR images were used. Necrosis was defined as non-perfused areas in the tumor and the necrotic volume was expressed as percentage of total volume. RESULTS: Out of 79 tumors, 10 (13%) showed no necrosis, 30 (38%) had 1-25% necrosis, 21 (27%) had 26-50% necrosis and the remaining 18 (23%) more than 50% necrosis. There was a correlation between tumor size and necrosis (p = 0.001): the median tumor volume increased with amount of necrosis (47 cm3 in non-necrotic tumors, 59 cm3 vs 280 cm3 vs 284 cm3 for tumors with 1-25% vs 26-50% vs > 50% necrosis). Tumor site (central location vs proximal extremities vs distal extremities) had no impact on necrosis (p = 0.71). 23 out of 79 patients had metastases (M1) at the time of diagnosis. The frequency of metastatic spread increased with the amount of necrosis: 1/10 (10%) patients with non-necrotic tumors had metastases vs 7/30 (23%) vs 6/21 (28%) vs 9/18 (50%) for tumors with 1-25% vs 26-50% vs > 50% necrosis. "Unfavorable" metastatic spread (bone or multiple metastases) was only noted in patients with high amount of necrosis (> 25% necrosis) whereas even large tumors did not show unfavorable metastases if they contained no or only small amounts of necrosis. All patients with non-necrotic tumors survived event-free during the observation period. Patients with necrotic tumors had a 3-year event-free survival of 55% (p = 0.06 vs tumors without necrosis). CONCLUSIONS: The presence of non-perfused (presumably necrotic) areas on pretreatment contrast-enhanced MR-images is associated with an increased risk of metastases, especially an unfavorable pattern of metastatic spread at diagnosis. This observation may be explained by a more aggressive biological behavior of hypoxic tumor cells. The small group of patients with non-necrotic tumors (13%) had an excellent prognosis suggesting that the absence of necrosis might be helpful in identifying a very favorable prognostic subgroup in Ewing tumors.

Adolescent↗

PubMed1995

Selective accumulation of strontium-89 in metastatic deposits in bone: radio-histological correlation.

The systemic administration of 89Sr has proven effective in the palliation of painful osseous metastases. Biodistribution studies with the gamma-emitter 85Sr suggest that both its uptake and retention are increased in bone metastases, where increased mineral turnover takes place. To study the pattern and nature of this process further, bones containing metastatic deposits were obtained from three patients who had previously been treated with 148 MBq of 89Sr. The bones were cut into 0.5-1.0 cm sections. The cut surfaces which faced together were marked with India ink, and adjacent sections were submitted for histology and autoradiography. Strontium deposition and retention were observed in regions which exhibited significant osteoblastic activity, mostly in areas adjacent to metastatic deposits, but also in subchondral and endosteal locations, as well as in an area corresponding to a pathological fracture with callus formation. With these exceptions, strontium deposition was not observed in histologically normal bone or within the marrow. Our findings demonstrate directly the selective nature of accumulation and retention of 89Sr and confirm previous clinical impressions.

Adenocarcinoma↗

PubMed2005

Metastatic and inflammatory cervical lymph nodes as analyzed by contrast-enhanced color-coded Doppler ultrasonography: quantitative dynamic perfusion patterns and histopathologic correlation.

Use of contrast-enhanced color-coded Doppler (ultra)sonography (CCDS) in evaluating enlarged lymph nodes has been subject to numerous attempts to define criteria for differentiation between benign and malignant lesions. Evaluation of dynamic perfusion patterns with contrast-enhanced CCDS in cervical lymph nodes offers new possibilities of differential diagnosis. A total of 28 patients with clinically enlarged lymph nodes were included in this study. Contrast-enhanced CCDS was performed on each patient. The color signals from nodes <15 mm in diameter were analyzed with a specialized computer program. Each node was later examined through immunohistochemical staining. Vascularization as shown by unenhanced CCDS was significantly greater in metastatic lymph nodes than in reactively enlarged lymph nodes (8.66% versus 2.81%; p = .01). The maximum vascularization area after contrast injection did not show any significant change (26.61% versus 28.63%; p = .75). Comparison of values obtained before and after contrast enhancement showed the largest relative increase in vascularization in inflammatory lymph nodes, from a factor of 19.55 to a factor of 10.03 (p = .025). Dynamic values such as contrast enhancement, behavior of dynamic values referred to time, and the evaluated vascularized area did not show any significant difference. The metastatic lymph nodes (5.46 versus 3.33; p = .007) predominantly consisted of large blood vessels. The increased vascularization in the unenhanced CCDS examination of metastatic lymph nodes seems to be associated with the increased number of large blood vessels. An increased vessel density, due to a greater number of total vessels, is related to an inflammatory process. Color Doppler mapping has been proven to depict useful aspects distinguishing benign from malignant lymph nodes of the neck; however, a definitive differentiation between lymph nodes involved with malignancy and inflammatory changes remains difficult.

Adult↗

PubMed1998

Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets.

Villin (V) is a glycoprotein of microvilli associated with rootlet formation. Most colonic adenocarcinomas have a V positive (+), cytokeratin (CK) 20 (+), CK7-negative (-) immunophenotype; most lung adenocarcinomas have a CK20(-), CK7(+) immunophenotype. The reports of villin immunoreactivity in lung adenocarcinoma range from 6% to 68% in studies using various fixations and varied anti-villin antibodies. Some lung adenocarcinomas have microvilli with rootlets leading to possible diagnostic confusion with metastatic colonic adenocarcinoma to lung. Nine primary lung adenocarcinomas with rootlets on ultrastructure (including four bronchioloalveolar carcinomas [BAC]), four metastatic lung adenocarcinomas with rootlets, nine metastatic colon adenocarcinomas to lung, and 10 randomly selected lung adenocarcinomas without rootlets (including five BAC), were immunostained with monoclonal antibodies to villin (1D2C3), CK7 (OV-TL12/30), and CK20 (Ks20.8) using a streptavidin peroxidase technique with heat-induced epitope retrieval. All primary lung adenocarcinomas with rootlets were CK7(+) CK20(-), and six of nine (67%) were V(+). Cytoplasmic villin positivity occurred in a diffuse--five of nine (56%), focal--two of nine (22%), or brush border pattern--two of nine (22%). Two of four metastatic lung adenocarcinomas with rootlets were V(+). One metastatic lung adenocarcinoma had a CK7(+), CK20(+), V(-) phenotype. All metastatic colonic adenocarcinomas were V(+), CK20(+), CK7(-), and 1 of 10 (10%) lung adenocarcinomas without rootlets was V(+), and all 10 were CK20(-), and CK7(+). In summary, villin positivity is more common in lung adenocarcinoma with rootlets (67%) than those without rootlets (10%). AU primary lung adenocarcinomas were CK7(+), CK20(-). The combination of villin, CK 7, and CK 20 is helpful in differentiating metastatic colon adenocarcinoma from lung adenocarcinoma with rootlets.

Adenocarcinoma↗

PubMed2004

Analysis of three-dimensional microarchitecture and degree of mineralization in bone metastases from prostate cancer using synchrotron microcomputed tomography.

Bone architecture and mineralization are generally considered to be important components of bone quality, and determine bone strength in conjunction with bone mineral density. Although the features of bone quality have recently been studied under conditions in which bone density decreases, such as osteoporosis, little is known in osteosclerotic diseases. In this study, we compared the trabecular bone microarchitecture and degree of mineralization between osteoblastic bone metastasis and degenerative osteosclerosis using synchrotron radiation microcomputed tomography (SR-microCT). Small cubes of lumbar vertebrae were excised postmortem from the sites of osteoblastic metastasis, degenerative osteosclerosis, and comparative sites of normal subjects without skeletal lesions. The samples were imaged at high spatial resolution (voxel size = 6 microm) using the SR-microCT system developed at the synchrotron facility (SPring-8), Hyogo, Japan. The three-dimensional (3D) image data were then analyzed for the morphological parameters and the degree of mineralization of bone (DMB). Trabecular bone in metastatic lesions showed a highly connected and isotropic network pattern compared with the normal samples. Although the trabecular surface was markedly irregular in osteoblastic metastases, no significant difference was found in the mean trabecular thickness (Tb.Th) between osteoblastic metastases and normal tissue. The DMB of trabeculae in metastatic lesions had a broader range and lower mean than that of the normal tissue. In contrast, trabecular bone in degenerative osteosclerotic lesions showed a similar degree of anisotropy (DA) and connectivity to the normal tissue, whereas the trabecular thickness was greater in the degenerative osteosclerotic lesions. No significant difference in DBM between degenerative osteosclerosis and normal tissue was detected. These results characterize the difference in bone quality between osteoblastic bone metastasis and degenerative osteosclerosis. Further study on the relationship between bone quality and bone strength in these osteosclerotic lesions would improve our understanding of the pathogenesis of bone fragility.

Adult↗

PubMed1988

Biochemical and cytogenetic studies of human lung cancers.

In ongoing studies, we have tested resected lung cancers from 41 men and 49 women; of those with primary lung cancer, 46 patients are free of disease and 35 have died of cancer or have persistent disease. Measurements and studies were as follows: total cellular deoxyribonucleic acid content by image analysis (n = 77); total genomic deoxyribonucleic acid methylation state and banding patterns from probed Southern blots (n = 36); radioimmunoassay for motilin, bombesin, gastrin, vasoactive intestinal peptide, and cholecystokinin (n = 18); and cytogenetic analysis (n = 39). All lung cancers were hyperploid. Adenocarcinomas and epidermoid carcinomas were generally hexaploid to nearly septaploid; comparisons by stage and histologic features suggested potential prognostic correlations. There was general hypomethylation of deoxyribonucleic acid (p less than 0.001). Deoxyribonucleic acid digests from restriction endonuclease Hpa II, when probed with deoxyribonucleic acid homologous to KPN, showed banding patterns that separated histologically indistinguishable primary adenocarcinomas and metastatic adenocarcinomas from one another. Cancers studied with radioimmunoassay were all negative for polypeptide hormones. Five cancers grew adequately in vitro to permit study of 190 detailed karyotypes (20 to 50 per tumor). Chromosome modal numbers ranged from 49 to 109. There were from 4 to 20 clearly abnormal marker chromosomes per tumor; abnormality derived from chromosome 1 was prevalent. Ten of 19 tumors xenotransplanted to nude mice were carried through two to five transplant generations without a change in histologic patterns.

Animals↗

PubMed1985

Prognostic implication of estrogen receptor content in breast cancer.

The cytosolic estrogen receptor (ER) content of the primary tumor was determined by isoelectric focusing in 170 consecutive women with unilateral breast cancer diagnosed in 1977 through 1980. No adjuvant treatment over and above surgery and radiotherapy was given. The overall corrected survival was not significantly (p greater than 0.05) higher in ER-rich (less than 0.1 nmol/g DNA) than in ER-poor tumors, but the median period from recurrence to death was longer in the former (16 months) than in the latter (10 months) group. The difference in disease-free survival (DFS) in favour of the ER-rich tumors achieved its maximum-about 15%-after two years (p less than 0.01). At prolonged follow-up, however, the curves converged and there was no significant difference when the whole six year period of observation was taken into account. In patients without axillary metastases the same pattern emerged, with earlier recurrences in ER-poor tumors and a difference in DFS between the two ER groups at two years (p less than 0.01) which was diminished after five years (p less than 0.05). The ER content provided no significant prognostic information in patients with axillary node metastases or locally advanced disease. We conclude from the present and other available data that the ER content in breast cancer would seem to be an indicator of growth rate rather than of metastatic potential and accordingly a predictor of the pattern of recurrence and length of disease-free survival rather than of long-term survival.

Adult↗

PubMed1994

Primary vs metastatic hepatic carcinoma. An immunohistochemical study of 34 cases.

The distinction between primary and metastatic hepatic epithelial malignant neoplasms can often be difficult if histologic features alone are used. The purpose of this study was to determine whether certain immunohistochemical markers could be used to aid in the diagnosis. The cases that were studied included 14 hepatocellular carcinomas, 10 cholangiocarcinomas, and seven metastatic adenocarcinomas; three cases of poorly differentiated carcinoma (not otherwise specified) were also studied. The antibodies that were chosen included alpha-fetoprotein, alpha 1-antitrypsin, monoclonal carcinoembryonic antigen, Leu-M1, B72.3, factor XIIIa, and Le(x). We found that the cases of hepatocellular carcinoma displayed cytoplasmic reactivity for alpha 1-antitrypsin, alpha-fetoprotein, and factor XIIIa. The cases of cholangiocarcinoma showed membranous and cytoplasmic reactivity for Le(x) but only cytoplasmic reactivity for Leu-M1 and B72.3, whereas the opposite pattern of staining was found in cases of metastatic adenocarcinoma. We conclude that immunohistochemical studies can be useful in the distinction of primary vs metastatic hepatic malignant neoplasms and recommend a panel of alpha 1-antitrypsin, alpha-fetoprotein, Leu-M1, B72.3, factor XIIIa, and Le(x).

Adenocarcinoma↗

PubMed1983

A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III).

A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.

Actuarial Analysis↗

PubMed2005

Deficiency in surface expression of E-selectin ligand promotes lung colonization in a mouse model of breast cancer.

Expression of sialyl Lewis(x) (sLe(x)) and sLe(a) on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly into the blood. We investigated the relative role of sLe(x) oligosaccharide in the dissemination of breast carcinoma, employing a spontaneous murine metastasis model. An sLe(x) deficient subpopulation of the 4T1 mammary carcinoma cell line was produced by negative selection using the sLe(x)-reactive KM93 MAb. This subpopulation was negative for E-selectin binding but retained P-selectin binding. Both sLe(x)-negative and -positive cells grew at the same rate; however, sLe(x)-negative cells spread more efficiently on plates and had greater motility in wound-scratch assays. Mice inoculated in the mammary fat pad with sLe(x)-negative and -positive variants produced lung metastases. However, the number of lung metastases was significantly increased in the group inoculated with the sLe(x)-negative variant (p = 0.0031), indicating that negative selection for the sLe(x) epitope resulted in enrichment for a subpopulation of cells with a high metastatic phenotype. Cell variants demonstrated significant differences in cellular morphology and pattern of tumor growth in primary and secondary tumor sites. These results strongly suggest that loss of sLe(x) may facilitate the metastatic process by contributing to escape from the primary tumor mass.

Animals↗

PubMed1998

[Effect of various forms of metastatic lymph node involvement on prognosis of squamous epithelial carcinomas of the upper aerodigestive tract].

BACKGROUND: Based on a new histo-morphological rating scheme, we assessed the impact on patient prognosis of lymph node metastasis of squamous cell carcinoma (SCC) in the head/neck area. Special attention was given to possible capsular rupture. METHOD: In a retrospective study, 111 patients with squamous cell carcinoma of the head and neck with concomitant cervical lymph node metastases were evaluated to determine the importance of lymph node capsular rupture on the occurrence of disseminated disease, loco-regional recurrence as well as survival rate. To cover the broad morphological spectrum of cervical metastatic disease, a newly developed scheme (differentiating seven different histo-morphological types of lymph node metastasis) was applied. On the basis of this scheme, every single metastatic lymph node received a score from one to seven. These single scores were then added to obtain a total score for every individual patient. These total scores were then divided into four groups. RESULTS: Synthesis of histo-morphological pattern of metastasis in combination with the number of metastatic lymph nodes showed highest concordance/significance in respect of disseminated disease (p = 0.0029), local recurrence (p = 0.0008) and regional lymph node metastasis (p = 0.0000) as well as survival rate (p = 0.0000). CONCLUSION: The newly introduced histological scheme seems to provide more accuiate and detailed information on the prognosis of SCC in the head and neck area.

Aged↗

PubMed1980

Eccentric cortical metastases to the skeleton from bronchogenic carcinoma.

Six cases of bronchogenic carcinoma metastatic to bone are reported in which the radiographic pattern of the skeletal metastases was remarkably similar. In each case, the osseous involvement was predominantly cortical, producing a focal area of geographic bone destruction. Predominant roentgen involvement of the cortex without evidence of extensive medullary destructon is unusual with metastatic lesions and has not, to our knowledge, been previously ascribed to a specific tumor. A brief review of distinctive features of metastatic skeletal lesions is given and a possible pathogenic mechanism offered to explain the unusual cortical location of the metastatic deposits in these cases.

Adult↗

PubMed1988

Patterns of breast relapse after local excision +/- radiotherapy for early stage breast cancer.

One hundred patients with breast recurrence have been identified from patients at the Royal Marsden Hospital, treated by local excision +/- radiotherapy for early stage primary invasive breast cancer between 1961 and 1985. The mean follow-up was 58 months (range 1 month - 19 years). In 74/100 patients, breast recurrence occurred within the breast parenchyma, was not associated with systemic relapse and carried a relatively good prognosis with a median survival of 77 months from the time of breast relapse. In 67 patients with parenchymal relapse in whom the site of relapse could be reliably compared with that of the original tumour, 60 (90%) patients developed recurrent tumours at or close to the primary site. In 24/100 patients, breast recurrence occurred in the overlying skin and in only two of these patients (2% of total) did recurrence actually occur within the scar tissue. Skin relapse was associated with systemic relapse and carried a relatively poor prognosis with a median survival of 36 months from the time of recurrence. The pattern of breast relapse was similar in irradiated and unirradiated patients. Skin relapse appears to be a manifestation of metastatic disease while parenchymal relapse may represent regrowth of primary tumour. This pattern of breast relapse questions the requirement for radiotherapy to the whole breast after local excision for early stage breast cancer.

Adult↗

PubMed1992

Histological changes during progression of adenoid cystic carcinoma.

Eight cases of adenoid cystic carcinoma were reviewed to determine whether and how the histological features of the tumour vary with the progress of the disease. The tumours were classified by their histological patterns as tubular, cribriform, trabecular or solid. The relative amount of each pattern seen in routine light microscopic sections was calculated histomorphometrically and compared in the primary tumour and recurrent and/or metastatic lesions in the same case. In the early stage, the tubular pattern predominated. Later, the highest percentage shifted to the cribriform, then to the trabecular and finally, in the late stage, to the solid pattern. There was no reverse direction of histological transformation from the solid to the tubular pattern. These results may help to explain previous reports that the tubular pattern usually represents a favourable prognosis, the solid pattern a poor prognosis and the cribriform pattern an intermediate prognosis.

Adult↗

PubMed2000

Skin equivalent: an attractive model to evaluate early melanoma metastasis.

The growth patterns and morphological phenotype of four human melanoma cell lines with different metastatic potentials were investigated in submerged and in air-exposed (skin equivalent) keratinocyte-melanoma cell co-cultures. In contrast to the submerged co-cultures, all four cell lines formed sharply demarcated tumour cell nests within the epidermal compartment of the skin equivalent model, with the morphology highly mimicking the in vivo situation. Differences among the melanoma cell lines tested were observed with respect to the number of clusters formed and the ability to exhibit invasive growth. Only the two metastatic cell lines were able to invade the dermal compartment. Screening of cellular adhesion molecules revealed that the expression patterns in different cell lines were heterogeneous and remained unchanged during the whole culture period, irrespective of whether the melanoma cells were located in the epidermal or dermal compartment. A correlation was found between expression of a lower number of different cellular adhesion molecules and the ability to acquire invasive growth capability. Our results indicate that melanoma cells exhibit a heterogeneous growth behaviour when co-cultured with human keratinocytes, and the air-exposed skin equivalent model was shown to be suitable for studying differences in growth patterns and potential invasive behaviour.

Air↗

PubMed1991

Complexity of expression of intermediate filament proteins, including glial filament protein, in endometrial and ovarian adenocarcinomas.

The expression patterns of intermediate filament proteins of primary and metastatic endometrial (n = 18) and ovarian (n = 24) adenocarcinomas were analyzed by immunocytochemistry using a panel of specific antibodies and by gel electrophoresis of cytoskeletal preparations, followed by immunoblotting. All cells of all endometrial adenocarcinomas studied contained the "simple epithelial"-type cytokeratins (CKs) 8, 18, and (mostly) 19, with variable numbers of cells also positive for CK 7 and vimentin. In addition, most of these tumors contained individual cells or groups of cells that were positive for the stratification-related CKs 4, 5, 6, 13, 14, and 17. The latter CKs were often associated with squamous cell foci, but were also found in some single (nonsquamous) tumor cells, indicative of early stages of squamous cell differentiation. Ovarian carcinomas of various histologic types and grades contained predominantly CKs 7, 8, 18, and 19. Serous, endometrioid, and anaplastic tumors, but not mucinous and clear cell tumors, also contained minor amounts of stratification-related CKs in variable combinations, mostly including CK 4. In all tumor types except mucinous tumors, vimentin was consistently detected in variable proportions of tumor cells which, however, were rather low in anaplastic carcinomas. Surprisingly, glial filament protein was detected in a minor proportion (< or = 20%) of tumor cells in seven of 14 serous and endometrioid ovarian carcinomas and in three of 18 endometrial carcinomas. These different intermediate filament expression patterns of müllerian duct-type carcinomas, only partly related to the morphologic appearance of the specific type of tumor, might reflect the multipotentiality of differentiation of müllerian duct-derived epithelia. Cytoskeletal features of potential diagnostic value, especially in metastatic carcinomas, are discussed.

Adenocarcinoma↗

PubMedDate not supplied

Differential expression patterns of the insulin-like growth factor 2 gene in human colorectal cancer.

Tumour development and metastasis are associated with altered gene expression profiles. The aim of this study was to identify the transcriptional differences in normal, tumour and metastatic tissue. We used oligonucleotide arrays to identify differential expression patterns of insulin-like growth factor 2 (IGF 2) between 139 primary colorectal tumour specimens and 42 tumour-adjacent mucosa specimens from colorectal cancer (CRC) patients. The expression levels of the IGF 2 gene were significantly increased in primary tumours compared with adjacent mucosae. This was concordant with our real-time RT-PCR quantification of 48 matched tumour mucosa samples. IGF 2 expression levels were also measured by RT-PCR quantitative analysis in 18 liver metastases and 10 normal tissues from patients without cancer. The mRNA levels were significantly under-expressed in liver metastases compared with either colorectal tumours or adjacent normal mucosae. The non- malignant normal tissue expressed significantly lower IGF 2 levels than adjacent normal tissue, and this was not due to a field effect originating from the tumour. In addition, our microarray data demonstrated that IGF 2 expression was down-regulated in sporadic microsatellite instability (MSI-H) CRC and parallels under-expression of hMLH1 and IGF 2 receptor genes in these patients. We conclude that IGF 2 plays an important role in CRC development. Also, individuals with loss of genomic imprinting (LOI) causing over-expression of IGF 2 may be at greater risk of developing CRC. However, this LOI may be reversed in MSI-H patients.

Colorectal Neoplasms↗

PubMed1979

Serum tyrosinase in malignant disease, its activity, and the electrophoretic patterns of the enzyme as carried by immunoglobulins'.

Serum tyrosinase activity in many persons with metastatic diseases was found to be significantly higher than activity in normal persons. The highest activity was observed in melanoma and breast carcinoma. The electrophoretic patterns of serum tyrosinase, resolved by electrophoresis of a serum tyrosinase fraction followed by incubation of the gel sample with L-dopa, and represented as sets of RF's of melanin bands, were characteristically different in melanoma, breast carcinoma, and certain other diseases. The RF's of melanin and protein bands in the serum enzyme preparations from melanoma patients were concisely defined. Further, some potent serum fractions inhibiting tyrosinase melanogenic activity have been obtained, and the presence of tyrosinase inhibitors in the serum enzyme preparation has also been demonstrated. More detailed exploration of these serum tyrosinase parameters may provide more specific and sensitive detection for certain malignant diseases.

Breast Neoplasms↗