Tissue microarrays for high-throughput molecular profiling of tumor specimens

Kononen, Juha; Bubendorf, Lukas; Kallioniemi, Anne; Bärlund, Maarit; Schraml, Peter; Leighton, Stephen B.; Torhorst, J.; Mihatsch, Michael J.; Sauter, Guido; Kallioniemi, Olli-P.

doi:10.1038/nm0798-844

Cited by 3,591 publications

(2,683 citation statements)

References 12 publications

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“…All samples were analysed in a tissue microarray (TMA) format. TMA construction was performed as described earlier (Kononen et al, 1998;Bavi et al, 2006). Briefly, tissue cylinders with a diameter of 0.6 mm were punched from representative tumor regions of each donor tissue block and brought into recipient paraffin block using a modified semi-automatic robotic precision instrument (Beecher Instruments, Woodland, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Abubaker¹,

Bavi²,

Al-harbi³

et al. 2008

Oncogene

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Activation of the phosphatidylinositol 3 0 -kinase (PI3K)/ AKT pathway results in an increase in cell proliferation and survival. Somatic mutations within the PI3K catalytic subunit, PIK3CA are common cause of increasing PI3K activity and are believed to be oncogenic in many cancer types. Few reports addressed the association between PIK3CA mutations and tumor progression specifically in microsatellite instable (MSI) colorectal cancer (CRC). In the present study, we have evaluated PIK3CA mutational status in a series of 410 Middle Eastern CRC and 13 colon cell lines to study the prevalence of PIK3CA mutations in MSI cases, PTEN expression in CRC and possibility of therapeutic targeting of this set of patients. PIK3CA mutations were found in four of the cell lines tested and 51 colorectal carcinomas (12.2%). Three of these four mutated cell lines were MSI. PTEN was inactivated in 66.1% of the CRC. Furthermore, we observed a strong association between PIK3CA mutations and MSI status (P ¼ 0.0046) while PTEN loss was more frequent in microsatellite stable (MSS) CRC (P ¼ 0.043). A high prevalence of genetic alterations in PI3K/AKT pathway in Saudi cohort of CRC, predominance of PIK3CA mutations in the MSI subgroup and their possible involvement in development/progression of this subset of CRC are some of the significant findings of our study.

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Section: Methodsmentioning

confidence: 99%

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Abubaker¹,

Bavi²,

Al-harbi³

et al. 2008

Oncogene

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“…From every patient, two representative regions were taken with a core tissue biopsy (diameter, 0.6 mm; height, 3-4 mm) and precisely arrayed into a new ''recipient'' paraffin block using a custom-built instrument. 12 After the block construction was completed, 4.0-lm sections of the resulting tumor tissue microarray block were cut for further analysis.…”

Section: Tissue Microarray Constructionmentioning

confidence: 99%

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx

Huber

Fritzsche

Züllig

et al. 2011

Intl Journal of Cancer

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In patients with early head and neck squamous cell carcinoma (HNSCC), occult lymph node metastasis is difficult to predict by clinical or pathological parameters. However, such parameters are necessary to select patients either for elective neck dissection or the sentinel lymph node (SLN) procedure. The membrane glycoprotein podoplanin is normally expressed in lymphatic endothelial cells. Recently, expression of podoplanin by cancer cells was demonstrated to promote tumor cell motility and tumor lymphangiogenesis in vitro. The value of cancer cell-expressed podoplanin was to be determined as a predictive marker for SLN metastasis in early HNSCC of the oral cavity and oropharynx. One hundred twenty patients with HNSCC of the oral cavity and oropharynx undergoing a SLN biopsy were enrolled in this prospective clinical trial of SLN biopsy. Cancer cell-expressed podoplanin was determined by immunohistochemistry using tissue microarrays. Podoplanin expression was quantified by the intensity reactivity score and categorized into expression and nonexpression. SLN examination revealed occult metastasis in 45 patients (37.5%). Twenty-nine of 120 (24.2%) primary HNSCC showed podoplanin expression. Podoplanin expression correlated significantly with SLN metastasis (p 5 0.029) and remained a significant predictor for lymph node status even after controlling for tumor stage (p 5 0.028). As a predictive marker for SLN metastasis, however, podoplanin expression reached a sensitivity of a mere 36% and a specificity of 83%. Podoplanin expression is associated with metastasis to lymph nodes in vivo. Podoplanin immunohistochemistry in early HNSCC of the oral cavity and oropharynx may help to select patients for the SLN procedure and to identify patients with increased risk for presence of occult lymph node metastasis in the neck.Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide and responsible for more than 7,800 deaths per year in the United States alone. 1 Despite improvements in surgical treatment and radiation technology over the last decades, survival has not significantly improved. A chief feature of malignant behavior is the capability of tumor cells to metastasize to other organs. Metastasis of many human cancers, including HNSCC, occurs primarily through the lymphatic system. The cellular mechanisms responsible for the acquisition of a metastatic phenotype include the adaptation to potential hostile environment (blood stream, lymph nodes and organ of metastasis). In addition, the ''tumor cell-to-tumor cell'' and ''tumor cell-to-stromal environment'' cross talk is recognized as an important condition for invasion and metastasis.Very recently, expression of the 38-kDa Type 1 transmembrane glycoprotein podoplanin has been shown to induce tumor lymphangiogenesis and enhance metastasis to lymph nodes. 2,3 Human podoplanin is expressed in various normal human tissues. Podoplanin is highly and specifically expressed in lymphatic endothelial cells, but not in blood vessel endothelium. 4,5...

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“…Tissue microarray has the advantage of simultaneous comparison of the expression patterns of many molecules in the same regions of tumors on the same slide. 28 Simultaneous staining on the same slide reduces variation due to technical manipulations, and simultaneous evaluation facilitates the application of identical criteria throughout the subjects to be evaluated. Furthermore, the tissue array is beneficial …”

Section: Discussionmentioning

confidence: 99%

Phenotypic composition of salivary gland tumors: an application of principle component analysis to tissue microarray data

et al. 2004

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The tissue organization of the salivary gland is complex, and a large number of salivary gland tumor entities with a broad morphologic spectrum are listed, creating tumor classification schema for the salivary glands that are difficult to understand. In the present study, we attempted to examine how the anatomical components of the salivary gland are associated with morphological subtypes of tumors. We selected a panel of 12 molecules, which labeled one or some of the components, with all of the markers covering every component of the salivary glands. Using tissue microarray, expression profiles of these molecules were examined in four representative spots from each of 88 salivary gland tumors. The resulting large data matrix was analyzed using principle component analysis (PCA). We considered the first three eigenvectors to be significant; as the eigenvalues were more than 1.0 and the cumulative proportion achieved was 67%. Comparison with expression patterns in normal tissue suggested that the three components represented myoepithelial differentiation, and luminal and basal cell phenotypes. Then, we compared the PCA results with individual morphologic subtypes. Individual subtypes were clustered among the three dimensions of the components. This implies that salivary gland tumors may be well characterized by using only three components.

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Tissue microarrays for high-throughput molecular profiling of tumor specimens

Cited by 3,591 publications

References 12 publications

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx

Phenotypic composition of salivary gland tumors: an application of principle component analysis to tissue microarray data

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