Lymphoid infiltration and prognosis in colorectal carcinoma

Jl, Svennevig; Lunde, O. C.; Holter, Jan Cato; Bjørgsvik, D.

doi:10.1038/bjc.1984.60

Cited by 171 publications

(57 citation statements)

References 16 publications

(9 reference statements)

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“…In this study, the expression levels of leukocyte- and lymphocyte-associated markers (CD45, CD4 and CD8) did not appear as a strong outcome predictor as the number of tumor-infiltrating lymphocytes shown in previous reports using immunohistochemistry [12–17]. One explanation is that the current study analyzed whole tumor tissues using array platforms, therefore it is not able to distinguish tumor-infiltrating lymphocytes from intravascular lymphocytes.…”

Section: Discussioncontrasting

confidence: 77%

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High level of chromosomal aberration in ovarian cancer genome correlates with poor clinical outcome

Cope

Shih

et al. 2013

Gynecologic Oncology

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Objectives Structural aberration in chromosomes characterizes almost all human solid cancers and analysis of those alterations may reveal the history of chromosomal instability. However, the clinical significance of massive chromosomal abnormality in ovarian high-grade serous carcinoma (HGSC) remains elusive. In this study, we addressed this issue by analyzing the genomic profiles in 455 ovarian HGSCs available from The Cancer Genome Atlas (TCGA). Methods DNA copy number, mRNA expression, and clinical information were downloaded from the TCGA data portal. A chromosomal disruption index (CDI) was developed to summarize the extent of copy number aberrations across the entire genome. A Cox regression model was applied to identify factors associated with poor prognosis. Genes whose expression was associated with CDI were identified by a 2-stage multivariate linear regression and were used to find enriched pathways by Ingenuity Pathway Analysis. Results Multivariate survival analysis showed that a higher CDI was significantly associated with a worse overall survival in patients. Interestingly, the pattern of DNA copy number alterations across all the chromosomes was similar between tumors with high and low CDI, suggesting they did not arise from different mechanisms. We also observed that expression of several genes was highly correlated with the CDI, even after adjusting for local copy number variation. We found that molecular pathways involving DNA damage response and mitosis were significantly enriched in these CDI-correlated genes. Conclusion Our results provide a new insight into the role of chromosomal rearrangement in the development of HGSC and the promise of applying CDI in risk-stratifying HGSC patients, perhaps for different clinical managements. The genes whose expression is correlated with CDI are worthy of further study to elucidate the mechanism of chromosomal instability in HGSC.

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Section: Discussioncontrasting

confidence: 77%

“…In addition, it has been reported that an increase of intratumoral lymphocytes is associated with better prognosis in some cancers [12–17]. Therefore, a lymphocytic infiltration is a possible confounding factor in the assessment of the association between CDI and prognosis.…”

Section: Resultsmentioning

confidence: 99%

High level of chromosomal aberration in ovarian cancer genome correlates with poor clinical outcome

Cope

Shih

et al. 2013

Gynecologic Oncology

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“…The importance of in®ltrating lymphocytes in colon cancer has long been appreciated since higher numbers of in®ltrating lymphocytes are associated with a more favourable outcome (Svennevig et al, 1984;Di Giorgio et al, 1992). This has led to extensive e orts towards immunotherapy for colon cancer.…”

Section: Discussionmentioning

confidence: 99%

NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps

et al. 2001

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The factors that govern the progression from colonic adenomatous polyp to colon cancer are poorly understood. The observation that NSAIDs act as chemopreventative agents and reduce the size of colonic polyps suggests the involvement of in¯ammatory signalling, but in¯ammatory signalling in colonic polyps has not been studied. We investigated the expression of the active forms of NF-kB, JNK and p38 MAPK using immunohistochemistry with activation speci®c antibodies in human colonic adenomas. We show that active NF-kB is seen in stromal macrophages that also express COX-2 and TNF-a, active JNK is seen in stromal and intraepithelial T-lymphocytes and periendothelial cells of new blood vessels, and active p38 MAPK is most highly expressed in macrophages and other stromal cells. These results demonstrate the presence of active in¯ammatory signal transduction in colonic polyps and that these are predominantly in the stroma. In the case of NF-kB this coincides with the cellular localisation of COX-2. These results support evidence that NSAIDs may act through e ects on stromal cells rather than epithelial cells. Oncogene (2001) 20, 819 ± 827.

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“…Between 1985 and 1995, several pathologists observed a seemingly increased infiltration of immune cells in routine immunostained patient tumor biopsy sections. Subsequent quantification of immune cell infiltration suggested a positive correlation between the extent of immune cell infiltration and the degree of malignancy 14 . Today, immunostaining remains one of the fundamental methods to analyze tumor-stroma interactions and continues to reveal correlative roles for different types of stromal cells in either promoting or reverting tumorigenesis 15,16 .…”

Section: Exploring the Role Of The Tumor Microenvironment: The Past Andmentioning

confidence: 99%

A journey to uncharted territory: new technical frontiers in studying tumor–stromal cell interactions

Guldner

Zhang

2015

Integr. Biol.

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The crosstalk between tumor cells and cells of the tumor stroma dictate malignant progression and represent an intriguing and viable anticancer therapeutic target. The successful development of therapeutics targeting tumor-stroma interactions is tied to the insight provided by basic research on such crosstalk. Tumor-stroma interactions can be transient and dynamic, and they occur within defined spatiotemporal contexts among genetically and compositionally heterogeneous populations of cells, yet methods currently applied to study the said crosstalk do not sufficiently address these features. Emerging imaging and genetic methods, however, can overcome limitations of traditional approaches and provide unprecedented insight into tumor-stroma crosstalk with unparalleled accuracy. The comprehensive data obtained by applying emerging methods will require processing and analysis by multidisciplinary teams, but the efforts will ultimately rejuvenate hope in developing novel therapies against pro-tumorigenic tumor-stroma crosstalk.

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Lymphoid infiltration and prognosis in colorectal carcinoma

Abstract: Images Figure 1 Figure 2

Cited by 171 publications

References 16 publications

High level of chromosomal aberration in ovarian cancer genome correlates with poor clinical outcome

High level of chromosomal aberration in ovarian cancer genome correlates with poor clinical outcome

NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps

A journey to uncharted territory: new technical frontiers in studying tumor–stromal cell interactions

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