A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma

Khor, Tin Oo; Gul, Yunus A.; Ithnin, Hairuszah; Seow, Heng Fong

doi:10.1007/s00384-005-0002-8

Cited by 44 publications

(41 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation suggests that restriction of cyclin D1 to the cytoplasm may allow suppression of cellular proliferation but requires a more rigorous investigation. Interestingly, a number of colorectal cancer studies have observed cytoplasmic cyclin D1 in tumour specimens (Palmqvist et al, 1998;Handa et al, 1999;McKay et al, 2000;Holland et al, 2001;Khor et al, 2006;Kuramochi et al, 2006) and at least one of these studies has reported that increased cytoplasmic cyclin D1 correlated with low proliferation (Palmqvist et al, 1998). This result is similar to our analyses ( Figure 4C), wherein tumours with predominately cytoplasmic cyclin D1 showed a significantly lower proliferative index.…”

Section: Discussionsupporting

confidence: 90%

“…The present finding that prostate cancer cells frequently exhibit cytoplasmic cyclin D1 is novel, but not without precedent. For example, elevated cyclin D1 with cytoplasmic cyclin D1 staining has been reported in many different tumour types, such as colorectal (Handa et al, 1999;Khor et al, 2006), pancreatic (Culhaci et al, 2005), lung (Dworakowska et al, 2005), thyroid (Temmim et al, 2006), and bladder (Sudo et al, 2003). Despite these observations only a handful of studies have addressed the functional consequence of cytoplasmic cyclin D1.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of differential cyclin D1 expression and localisation in prostate cancer

et al. 2007

View full text Add to dashboard Cite

Cyclin D1 is a critical regulator of androgen-dependent transcription and cell cycle progression in prostate cancer cells. Despite the influence of D-type cyclins on prostate cancer proliferation, few studies have examined the expression of cyclin D1 in localised tumours or challenged its relevance to disease progression. Cyclin D1 status was characterised using immunohistochemistry in 38 non-neoplastic prostate samples, 138 primary human prostate carcinomas, and three lymph node metastatic specimens. Relevance of cyclin D1 to preoperative prostate-specific antigen (PSA) levels, Ki-67 index, and p21 Cip1 status was also examined. Cyclin D1-positive phenotype was increased in primary carcinoma compared to non-neoplastic tissue, and was evident in all lymph node metastases cases. Interestingly, at least three distinct localisation patterns were observed in the cyclin D1-positive cohort, wherein cytoplasmic localisation was identified in a large fraction, and this pattern was predominant in lower grade tumours. Relevance of altered cyclin D1 status was observed, wherein cyclin D1-positive tumours were associated with low preoperative PSA levels, consistent with in vitro reports that cyclin D1 may alter the expression of this tumour marker. Moreover, tumours with predominantly cytoplasmic cyclin D1 showed the lowest Ki-67 index, whereas nuclear cyclin D1 was associated with higher grade, elevated Ki-67, and increased nuclear p21 Cip1 . These data demonstrate that differential cyclin D1 status may influence clinicopathological parameters, and reveal new insight as to the regulation and potential consequence of cyclin D1 expression in prostate cancer.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Impact of differential cyclin D1 expression and localisation in prostate cancer

et al. 2007

View full text Add to dashboard Cite

show abstract

“…They demonstrated a strong Wnt-1 staining in the normal colonic epithelium, while in the majority of primary tumors the expression was decreased. By contrast, Khor et al (16) revealed in 47 colorectal tissue samples that intratumoral protein expression of Wnt-1 was significantly increased in the primary tumor compared with the normal epithelium. Finally, Holcombe et al (17) revealed in CRC that Wnt-1 is expressed equally and strongly in normal and malignant colon tissues.…”

Section: Discussionmentioning

confidence: 86%

Expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: Associations with the primary tumor

et al. 2015

View full text Add to dashboard Cite

Abstract. The wingless-type mouse mammary tumor virus integration site family (Wnt) pathway plays a major role in the carcinogenesis of colorectal cancer (CRC). Its most important effector, the nuclear β-catenin, influences not only transcription but also the proliferation and dedifferentiation of the colonic mucosa. This induces an epithelial-mesenchymal transition which ultimately can lead to the development of cancer and the formation of metastases. However, little is known about the exact interaction and context-sensitive expression of Wnt-pathway effectors in the primary tumor and corresponding metastasis. Therefore, this study assessed the expression of the three most important effectors of the Wnt pathway, β-catenin, adenomatous polyposis coli (APC) and Wnt-1, in the primary tumor and corresponding metastasis of patients with CRC. Immunohistochemical staining of β-catenin, APC and Wnt-1 was performed in paraffin-embedded tissue samples of the primary tumor, and the corresponding hepatic and nodal metastasis samples from 24 patients with metastatic CRC. Isotype antibodies were used as negative controls. The results were visualized using the ABC-method. Analysis of the primary tumor comprised of a separate evaluation of the central tumor area as well as the invasion front. There was a significant overexpression of nuclear β-catenin at the tumor invasion front (P<0.001). Compared to normal colonic mucosa, expression of cytoplasmic β-catenin was significantly higher in the primary tumor (P<0.001) as well as all the corresponding hepatic and lymphatic metastases (hepatic metastases, P=0.001; nodal metastases, P=0.017). By contrast, APC expression was significantly lower in all analyzed tumor compartments compared with normal colonic mucosa (primary tumor, P=0.022; hepatic metastases, P=0.006; nodal metastases, P=0.012). Finally, Wnt-1 protein expression was significantly lower in liver metastases but not in the primary tumor or lymphatic metastases compared with normal colonic mucosa (P=0.003). The present study demonstrates that the major Wnt-effector proteins, β-catenin, APC and Wnt-1, are heterogeneously expressed in the primary tumor and corresponding hepatic as well as nodal metastases of patients with CRC. This context-sensitive diverse expression of Wnt-effector proteins may be important for future individualized targeted therapies.

show abstract

“…Posterior studies using RT-PCR and immunohistochemistry involving newer antibodies and reagents have revealed the presence of survivin in non-tumorous tissues, especially in colon mucosa adjacent to carcinomas (21,22,52). One of these experiments involved the same reagent used in the present study (52).…”

Section: Discussionmentioning

confidence: 91%

Immunoexpression of inhibitors of apoptosis proteins and their antagonist SMAC/DIABLO in colorectal carcinoma: Correlation with apoptotic index, cellular proliferation and prognosis

Lima

Costa²,

Barrezueta³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. The inhibitors of apoptosis proteins (IAPs) act by directly blocking cleaved caspase-3 (XIAP) or the protein SMAC/DIABLO, an antagonist. The inhibition of XIAP activity or the increase of SMAC activity might improve the therapeutic response of the patients. This work evaluated the immunoexpression of IAPs and SMAC in colorectal carcinoma and their correlation with apoptotic index (AI), cellular proliferation, p53 protein immunoexpression and patient survival rate. TMA paraffin blocks were made with colorectal cancer tissue and adjacent non-tumorous mucosa of 130 patients, not submitted to radio or chemotherapy. Sections of 4 μm were processed by immunohistochemistry for survivin, XIAP, cIAP-1, cIAP-2 and SMAC, and the immunoexpression scores were obtained. They were correlated between each other and with the AI obtained by anticleaved caspase-3 and M30 (cleaved cytokeratin-18) antibodies, the cellular proliferation index, p53 protein immunoexpression and patient survival data. Direct correlation occurred between the four IAPs studied in tumor and nontumorous mucosa tissues. SMAC, survivin, cIAP-1 and cIAP-2 were positively correlated with tumoral tissue AI. Cellular proliferation and p53 immunoexpression was positively correlated with XIAP, SMAC and cIAP-1 scores. Low cIAP-1 immunoexpression showed a tendency for correlation with shorter patient survival. Equilibrium between the activities of IAPs and SMAC was demonstrated by the direct correlation between their immunoexpression. Correlation between SMAC and AI confirmed the pro-apoptotic activity of this protein. XIAP showed no inverse correlation with AI. XIAP, SMAC and cIAP-1 play a role in colorectal tumorigenesis, as demonstrated by their direct correlation with cellular proliferation and p53 protein. The tendency for correlation between low cIAP-1 immunoexpression and survival might indicate a role for this protein as a prognostic marker in colorectal cancer.

show abstract

A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma

Cited by 44 publications

References 27 publications

Impact of differential cyclin D1 expression and localisation in prostate cancer

Impact of differential cyclin D1 expression and localisation in prostate cancer

Expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: Associations with the primary tumor

Immunoexpression of inhibitors of apoptosis proteins and their antagonist SMAC/DIABLO in colorectal carcinoma: Correlation with apoptotic index, cellular proliferation and prognosis

Contact Info

Product

Resources

About