TRARESA: a tissue microarray-based hospital system for biomarker validation and discovery

Das, Kakoli; Omar, Mohd Feroz Mohd; Ong, Chee Wee; Rashid, Suhaimi Bin Abdul; Peh, Bee Keow; Putti, Thomas Choudary; Tan, Puay Hoon; Chia, Kee Seng; Teh, Ming; Shah, Nilesh; Soong, Richie; Salto-Tellez, Manuel

doi:10.1080/00313020802198101

Cited by 21 publications

(18 citation statements)

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“…Three sets of ovarian cancer tissue microarrays containing three cores from 198 primary ovarian cancer cases, three sets of breast tissue microarrays containing three cores from 300 breast cancer cases, and one set of gastric tissue mircroarrays containing 142 gastric cancer cases were constructed as detailed in previous studies. 18,19 A 1.0-mm-diameter needle was used to punch a donor core from morphologically representative areas of a donor tissue block. The core was subsequently inserted into a recipient paraffin block using a MTA-1 Manual Tissue Arrayer (Beecher Instruments, WI).…”

Section: Methodsmentioning

confidence: 99%

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

Stewart¹,

James

McCluggage

et al. 2015

Modern Pathology

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The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers. Immunohistochemical analysis using a TMA platform revealed WLS overexpression in a subset of ovarian, gastric, and breast tumors; this overexpression was associated with poorer clinical outcomes in gastric cancer (P ¼ 0.025). In addition, a strong correlation was observed between WLS expression and human epidermal growth factor receptor 2 (HER2) overexpression. Indeed, 100% of HER2-positive intestinal gastric carcinomas, 100% of HER2-positive serous ovarian carcinomas, and 64% of HER2-positive breast carcinomas coexpressed WLS protein. Although HER2 protein expression or gene amplification is an established predictive biomarker for trastuzumab response in breast and gastric cancers, a significant proportion of HER2-positive tumors display resistance to trastuzumab, which may be in part explainable by a possible mechanistic link between WLS and HER2. Modern Pathology (2015) 28, 428-436; doi:10.1038/modpathol.2014 published online 26 September 2014 The molecular mechanisms controlling the maturation and secretion of WNT proteins in the cells responsible for their production are attracting considerable attention. Wntless (WLS) (also known as GPR177 and Evi) was recently discovered as a key modulator of WNT protein secretion. [1][2][3] This multipass transmembrane protein localizes to compartments of the secretory pathway including the Golgi apparatus, endosomes, and plasma membrane. WLS acts as a WNT cargo receptor, shuttling palmitoylated Wnts from the endoplasmic reticulum to the plasma membrane, and it is required for exocytosis of WNT proteins from the WNT-producing cells. 4 In contrast to most other components of the WNT signaling pathway, only a single WLS gene exists in vertebrate genomes. WLS appears to be required for the secretion of all WNT proteins in both the canonical and noncanonical WNT pathways. 5 Augustin et al 6 recently demonstrated that WLS is highly overexpressed in malignant astrocytomas, indicating that the aberrant release of canonical and noncanonical WNT is a potential driver of glioma tumorigenesis required for proliferation, survival, and migration of glioma cells. Their work raises the question of whether WLS has a similar role in other cancers known to have aberrant activation of WNT signaling, including ovarian, gastric, and breast cancers. [7][8][9][10][11][12][13][14][15]

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Section: Methodsmentioning

confidence: 99%

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

Stewart¹,

James

McCluggage

et al. 2015

Modern Pathology

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“…18,19 Briefly, a needle with 0.6-mm diameter was used to punch a donor core from morphologically representative areas of a donor tissue block. The core was subsequently inserted into a recipient paraffin block using an ATA-100 tissue arrayer (Chemicon, USA).…”

Section: Tissue Microarraysmentioning

confidence: 99%

CD133 expression predicts for non-response to chemotherapy in colorectal cancer

et al. 2010

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The cancer stem cell hypothesis may explain why conventional chemotherapies are unable to fully eradicate cancers. In this study, we examined both the prognostic and predictive significance of putative cancer stem cell markers in colorectal cancer. In this study, immunohistochemistry for three candidate cancer stem cell markers (CD133, Oct-4 and Sox-2) and for six other postulated prognostic markers (CK7, CK20, Cox-2, Ki-67, p27 and p53) were performed using tissue microarrays containing 501 primary colorectal cancer cases. Receiveroperating characteristic analysis was used to determine cut-off scores for positive protein expression. Multivariate analysis revealed that positive expression for CD133 and Oct-4 was associated with significantly worse survival in patients treated by surgery alone (P ¼ 0.023 and Po0.001, respectively) and in patients treated with 5-fluorouracil-based chemotherapy (P ¼ 0.001 and P ¼ 0.021, respectively). Stage III patients with negative CD133 expression showed an apparent survival benefit from 5-fluorouracil treatment (P ¼ 0.002), but not those with positive CD133 expression. Positive expression of CD133 was also associated with poorer clinical response to chemotherapy in stage IV patients (P ¼ 0.006). In summary, the putative cancer stem cell markers CD133 and Oct-4 showed strong prognostic significance in colorectal cancer. Our results show for the first time that CD133 þ colorectal tumors are more resistant to 5-fluorouracil-based chemotherapy.

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“…Immunohistochemistry was performed on TMA constructed from formalin-fixed paraffin-embedded (FFPE) prostate tumors and matched benign tissues following the protocol described previously (Zhang et al 2003, Salto-Tellez et al 2007, Das et al 2008b. Sections (4 mm) were deparaffinized and rehydrated using graded alcohols before heating with antigen retrieval solution (pH 6) at 120 8C for 5 min, followed by peroxidase blocking for 10 min at room temperature.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Differential expression of steroid 5α-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

Das

Lorena²,

Ng³

et al. 2010

Endocrine-Related Cancer

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The biological role of steroid 5a-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (nZ62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (PZ0.02), higher cancer stage (PZ0.01), and higher serum prostate specific antigen (PSA) levels (PZ0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (PZ0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor b 1 (TGFB1), endothelin (EDN1), TGFa (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 mM). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors.

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TRARESA: a tissue microarray-based hospital system for biomarker validation and discovery

Cited by 21 publications

References 50 publications

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression

CD133 expression predicts for non-response to chemotherapy in colorectal cancer

Differential expression of steroid 5α-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

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