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Histopathological features predict metastatic potential in locally advanced colon carcinomas.

Jayasinghe C, Simiantonaki N, Kirkpatrick CJ - BMC Cancer (2015)

Bottom Line: Metastatic dissemination can exist before a pathologically and clinically detectable manifestation.In the multivariate analysis, with the exception of large vessel density, these pathomorphological features were independent risk factors for lymphogenous metastasis (p = 0.023, p = 0.017, p = 0.037, p = 0.012, respectively) with a good discrimination ability (AUC of 0.853).Features associated with distant metastasis in the univariate analysis included high tumor budding (p = 0.002), low intratumoral small vessel density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048) and abundant necrosis (p = 0.073).

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101, Mainz, Germany. c.jayasinghe@gmx.de.

ABSTRACT

Background: Metastatic dissemination can exist before a pathologically and clinically detectable manifestation. The structural heterogeneity of colon cancer (CC) in histological sections with respect to the morphology of tumor aggressiveness and composition of the tumor microenvironment raises the question of whether the microscopical tumor architecture enables a discrimination of groups with different metastatic potential. This would result in an assessment of the prognosis and provision of an ancillary tool for the therapeutic management after surgery, beside the estimation of the local tumor extent.

Methods: In order to identify predictive biomarkers for metastasis of locally advanced CC, which can easily be integrated into the pathologist's daily routine diagnostic activity, we determined tumor budding, peritumoral inflammation, extent of desmoplasia and necrosis, density of macro- and microvascular blood vessels and functional state of lymphatics in the tumor center, invasive margin and tumor-free surrounding tissue in 86 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic, subserosa-invasive CC.

Results: Features influencing nodal metastasis in the univariate analysis included high tumor budding (p = 0.004), high large vessel density in the subserosa (p = 0.043), abundant desmoplasia (p = 0.049), non-finger-like desmoplastic pattern (p = 0.051) and absent lymphocellular intratumoral inflammation (p = 0.084). In the multivariate analysis, with the exception of large vessel density, these pathomorphological features were independent risk factors for lymphogenous metastasis (p = 0.023, p = 0.017, p = 0.037, p = 0.012, respectively) with a good discrimination ability (AUC of 0.853). Features associated with distant metastasis in the univariate analysis included high tumor budding (p = 0.002), low intratumoral small vessel density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048) and abundant necrosis (p = 0.073). In the multivariate analysis only tumor budding was an independent predictor for haematogenous metastasis (p = 0.007) with a good discrimination ability (AUC of 0.829).

Conclusions: Thus, mainly tumor budding but also the described structural characteristics of the peritumoral tissue appears to reflect the metastatic potential of locally advanced CC and therefore should be stated in pathological reports.

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Related in: MedlinePlus

Vascular densitiy in three different zones in non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. Box plot of large vessel density (LVD), small vessel density (SVD) and microvascular vessel density (MVD) in zone 1, zone 2 and zone 3 between non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. The dark lines denote the median and the open diamond the mean value of each group.
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Fig3: Vascular densitiy in three different zones in non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. Box plot of large vessel density (LVD), small vessel density (SVD) and microvascular vessel density (MVD) in zone 1, zone 2 and zone 3 between non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. The dark lines denote the median and the open diamond the mean value of each group.

Mentions: Large vessels, essential for sufficient blood flow, were seen not only in zone 3 but also intratumorally and along the tumor front (Figures 3 and 4). It should be emphasized that these arteries showed arteriosclerotic changes, characterizing preexistent vessels. In zone 1 and 2 no significant correlations were found between LVD and metastatic status. In zone 3 nodal positive cases were associated with a significantly higher LVD compared to cases without metastasis (p = 0.043) (Table 2). LVD in N0/M0 ranged from 0 – 5.0/25 mm2 with the median at 0.5/25 mm2 and in N+ from 0 – 5.5/25 mm2 with the median at 1,3/25 mm2 (Figure 3).Figure 3


Histopathological features predict metastatic potential in locally advanced colon carcinomas.

Jayasinghe C, Simiantonaki N, Kirkpatrick CJ - BMC Cancer (2015)

Vascular densitiy in three different zones in non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. Box plot of large vessel density (LVD), small vessel density (SVD) and microvascular vessel density (MVD) in zone 1, zone 2 and zone 3 between non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. The dark lines denote the median and the open diamond the mean value of each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307171&req=5

Fig3: Vascular densitiy in three different zones in non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. Box plot of large vessel density (LVD), small vessel density (SVD) and microvascular vessel density (MVD) in zone 1, zone 2 and zone 3 between non-metastatic (N0/M0) and lymphogenous metastatic (N+) CC. The dark lines denote the median and the open diamond the mean value of each group.
Mentions: Large vessels, essential for sufficient blood flow, were seen not only in zone 3 but also intratumorally and along the tumor front (Figures 3 and 4). It should be emphasized that these arteries showed arteriosclerotic changes, characterizing preexistent vessels. In zone 1 and 2 no significant correlations were found between LVD and metastatic status. In zone 3 nodal positive cases were associated with a significantly higher LVD compared to cases without metastasis (p = 0.043) (Table 2). LVD in N0/M0 ranged from 0 – 5.0/25 mm2 with the median at 0.5/25 mm2 and in N+ from 0 – 5.5/25 mm2 with the median at 1,3/25 mm2 (Figure 3).Figure 3

Bottom Line: Metastatic dissemination can exist before a pathologically and clinically detectable manifestation.In the multivariate analysis, with the exception of large vessel density, these pathomorphological features were independent risk factors for lymphogenous metastasis (p = 0.023, p = 0.017, p = 0.037, p = 0.012, respectively) with a good discrimination ability (AUC of 0.853).Features associated with distant metastasis in the univariate analysis included high tumor budding (p = 0.002), low intratumoral small vessel density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048) and abundant necrosis (p = 0.073).

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101, Mainz, Germany. c.jayasinghe@gmx.de.

ABSTRACT

Background: Metastatic dissemination can exist before a pathologically and clinically detectable manifestation. The structural heterogeneity of colon cancer (CC) in histological sections with respect to the morphology of tumor aggressiveness and composition of the tumor microenvironment raises the question of whether the microscopical tumor architecture enables a discrimination of groups with different metastatic potential. This would result in an assessment of the prognosis and provision of an ancillary tool for the therapeutic management after surgery, beside the estimation of the local tumor extent.

Methods: In order to identify predictive biomarkers for metastasis of locally advanced CC, which can easily be integrated into the pathologist's daily routine diagnostic activity, we determined tumor budding, peritumoral inflammation, extent of desmoplasia and necrosis, density of macro- and microvascular blood vessels and functional state of lymphatics in the tumor center, invasive margin and tumor-free surrounding tissue in 86 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic, subserosa-invasive CC.

Results: Features influencing nodal metastasis in the univariate analysis included high tumor budding (p = 0.004), high large vessel density in the subserosa (p = 0.043), abundant desmoplasia (p = 0.049), non-finger-like desmoplastic pattern (p = 0.051) and absent lymphocellular intratumoral inflammation (p = 0.084). In the multivariate analysis, with the exception of large vessel density, these pathomorphological features were independent risk factors for lymphogenous metastasis (p = 0.023, p = 0.017, p = 0.037, p = 0.012, respectively) with a good discrimination ability (AUC of 0.853). Features associated with distant metastasis in the univariate analysis included high tumor budding (p = 0.002), low intratumoral small vessel density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048) and abundant necrosis (p = 0.073). In the multivariate analysis only tumor budding was an independent predictor for haematogenous metastasis (p = 0.007) with a good discrimination ability (AUC of 0.829).

Conclusions: Thus, mainly tumor budding but also the described structural characteristics of the peritumoral tissue appears to reflect the metastatic potential of locally advanced CC and therefore should be stated in pathological reports.

Show MeSH
Related in: MedlinePlus