Non-invasive detection of malignancy by identification of unusual CD44 gene activity in exfoliated cancer cells

Matsumura, Yasuhiro; Hanbury, Damian; Smith, Joseph; Tarin, David

doi:10.1136/bmj.308.6929.619

Cited by 93 publications

(59 citation statements)

References 15 publications

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“…We have previously shown that elevated quantities of unusual CD44 transcripts and protein isoforms are detectable in exfoliated cells present in naturally micturated urine from bladder cancer patients (Matsumura et al, 1994). Moreover, exfoliated carcinoma cells in colon luminal washings were also shown to be detectable in about 73% of cases, when using CD44 exons 11 and 12 as detection markers .…”

Section: Discussionmentioning

confidence: 98%

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

Yoshida

Sugino²,

Goodison³

et al. 1997

Br J Cancer

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Summary Telomerase is a ribonucleoprotein capable of replacing telomeric DNA sequences that are lost at each cell division. Under normal circumstances, it is active in rapidly dividing embryonic cells and in stem cell populations but not in terminally differentiated somatic cells. Much attention has recently focused on the hypothesis that activity of this enzyme is necessary for cells to become immortal. This predicts that telomerase activity should be detectable in malignant cells and tissues but not in their normal counterparts, which slowly senesce and die. In accordance with this notion, telomerase activity has been reported in a wide range of malignancies, including those of the gastrointestinal tract, breast and lung. In the present study, we used a polymerase chain reaction (PCR)-based assay for telomerase activity, designated the 'telomeric repeat amplification protocol (TRAP)', to examine initially 35 colonic carcinomas, their corresponding normal tissues and 12 inflammatory bowel disease (IBD) lesions. We detected strong enzyme activity in 32 (92%) of the 35 colon carcinomas while there was no activity in 30 (86%) of 35 matched normal colonic tissue specimens and only very weak activity in the remainder. Four of seven specimens of ulcerative colitis and two of five Crohn's disease lesions were negative, and the rest were only weakly positive. These results led us to examine whether telomerase could be detected in carcinoma cells exfoliated into the colonic lumen. We assayed lysates of exfoliated cells in luminal washings from colectomy specimens of 15 patients with colon carcinoma and nine with IBD. Telomerase activity was detected in washings from 9 (60%) of the 15 colon carcinoma cases but not in any from cases with IBD, suggesting that it can be a good marker for the detection of colon carcinoma, possibly even in non-invasively obtained samples.

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Section: Discussionmentioning

confidence: 98%

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

Yoshida

Sugino²,

Goodison³

et al. 1997

Br J Cancer

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“…Qualitative and quantitative changes in expression of CD44 have been demonstrated in vitro in the vascular dissemination of melanoma (Birch et al, 1991) and lymphoma cells (Sy et al, 1991), and in the migration of rat pancreas carcinoma cells on the extracellular matrix (Günthert et al, 1991). In vivo, enhanced or upregulation of CD44 (core or variant) expression has been found to be related to tumour progression in breast (Joensuu et al, 1993), colorectal (Abbasu et al, 1993a;Tanabe et al, 1993;Wielenga et al, 1993), gastric (Heider et al, 1993a;Mayer et al, 1993), cervical (Dall et al, 1994) and bladder (Matsumura et al, 1994;Southgate et al, 1995) carcinomas, non-Hodgkin's lymphoma (Koopman et al, 1993) and brain tumours (Terpe et al, 1993). Conversely, loss of or reduction in expression of CD44v isoforms is associated with disease progression in squamous cell (Salmi et al, 1993) and endometrial carcinomas (Fujita et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Altered expression of CD44 has been observed in a large number of tumours of adult life (Matsumura and Tarin, 1992;Abbasu et al, 1993;Heider et al, 1993a;1993b;Joensuu et al, 1993;Tanabe et al, 1993;Matsumura et al, 1994;Penno et al, 1994;Southgate et al, 1995;Harwood et al, 1996;Nagabhushan et al, 1996) and in the paediatric malignancy neuroblastoma (Favrot et al, 1993;Gross et al, 1994Gross et al, , 1995Shtivelmann and Bishop, 1991). The aim of this study was to document the pattern of expression of CD44 by rhabdomyosarcomas and to determine the relationship of CD44 expression to prognosis.…”

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confidence: 99%

Expression of CD44 by rhabdomyosarcoma: a new prognostic marker?

et al. 1999

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SummaryThe expression pattern of CD44 standard and variant isoforms are prognostically significant in a number of malignancies. The aim of this study was to evaluate the role of the standard isoform of CD44 in predicting the clinical behaviour of rhabdomyosarcoma. Immunohistochemical analysis of CD44 was undertaken using a panel of antibodies recognizing the three core domains of the CD44 molecule. Labelling was repeated in triplicate and reported blind with respect to histological type and outcome. Tumours were characterized as positive in more than 60% of tumour cells labelled and negative if less than 40% of tumour cells labelled. Tumours with 40-60% of tumour cells labelling were considered indeterminate. Eleven of 20 favourable histology tumours were positive for CD44 compared with one of seven unfavourable tumours (P = 0.07). Eleven of 12 patients with CD44-positive tumours are alive in first remission compared with five of 15 CD44-negative tumours (P = 0.001). Expression of CD44 correlates directly with prognosis; however, larger studies are required so that multivariate analysis can be undertaken.

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“…Ten of them are constitutively expressed on almost all cell types to produce a heavily glycosylated 85-90 kD isoform known as the standard form (CD44st). The remaining exons can be alternatively spliced to produce various isoforms, [5][6][7] which are called CD44 variants (CD44v). Although in humans the functions of CD44v remain unclear, they may play an important role in the growth and metastasis of several kinds of tumors.…”

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confidence: 99%

Clinicopathological Significance of Expression of CD44 Variants in Head and Neck Squamous Cell Carcinoma

Kanke

Fujisawa

Kameyama

et al. 2000

Japanese Journal of Cancer Research

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Splice variants of the cell surface glycoprotein CD44 have been reported to be associated with the progression of various human tumors. The aim of this study is to determine the correlation between the expression of CD44 isoforms, especially CD44 variant 2 (CD44v2), and the clinicopathological features of head and neck squamous cell carcinomas (HNSCCs). The expression of CD44 isoforms was evaluated immunohistochemically in paraffin-embedded tissues from 89 primary lesions, using monoclonal antibodies against CD44 standard (CD44st), CD44 variant 6 (CD44v6) and CD44v2. Cancer tissues from 89 (100%), 85 (95.5%) and 59 (66.3%) patients showed positive immunoreactivity for CD44st, CD44v6 and CD44v2, respectively. A significant correlation was observed between the down-regulation of CD44v2 and poorer differentiation of the tumor cells (P = = = =0.02). We could not find any significant correlation between the expression of CD44v2 and T stage or N stage (lymph node status). However, the rate of positive cervical lymph node metastasis tended to increase with reduced expression of CD44v2 (P = = = =0.08). Down-regulation of CD44v2 expression was correlated with shorter overall survival (P = = = =0.01). Furthermore, Cox's multivariate analysis revealed that only CD44v2 expression and lymph node status were independent prognostic factors. These findings suggest that down-regulation of CD44v2 expression may be one of the biological markers for the degree of malignancy in HNSCCs.

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Non-invasive detection of malignancy by identification of unusual CD44 gene activity in exfoliated cancer cells

Abstract: Objective-To investigate non-invasive detection of cancer by testing for unusual CD44 gene activity in a clinical sample as an indicator of exfoliated tumour cells.

Cited by 93 publications

References 15 publications

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

Expression of CD44 by rhabdomyosarcoma: a new prognostic marker?

Clinicopathological Significance of Expression of CD44 Variants in Head and Neck Squamous Cell Carcinoma

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