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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

Morphology of blood and lymphatic vessels in CC. (A) Large vessels (sm-actin (SMA), x100), (B) small vessels (SMA, x200) and (C) microvascular vessels (CD31, x40) in CC. (D) Altered blood vessels with discontinuously hypoplastic smooth muscle cell layer (SMA, x200). (E) Intratumoral compressed lymphatic vessels (D2-40, x200). (F) Lymphatic vessels at the tumor periphery with open lumina (D2-40, x100).
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Fig2: Morphology of blood and lymphatic vessels in CC. (A) Large vessels (sm-actin (SMA), x100), (B) small vessels (SMA, x200) and (C) microvascular vessels (CD31, x40) in CC. (D) Altered blood vessels with discontinuously hypoplastic smooth muscle cell layer (SMA, x200). (E) Intratumoral compressed lymphatic vessels (D2-40, x200). (F) Lymphatic vessels at the tumor periphery with open lumina (D2-40, x100).

Mentions: To evaluate the histological vascularization pattern of CC we performed immunostaining for the pan-endothelial marker CD31 and smooth muscle marker sm-actin which produced very strong signals in blood vessels of various sizes, that is, large and small vessels as well as microvasculature (Figure 2A-C). The distribution and density of these different sized vessels were analyzed in the tumor center, tumor margin and tumor-free surrounding tissue.Figure 2


Histopathological features predict metastatic potential in locally advanced colon carcinomas.

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

Morphology of blood and lymphatic vessels in CC. (A) Large vessels (sm-actin (SMA), x100), (B) small vessels (SMA, x200) and (C) microvascular vessels (CD31, x40) in CC. (D) Altered blood vessels with discontinuously hypoplastic smooth muscle cell layer (SMA, x200). (E) Intratumoral compressed lymphatic vessels (D2-40, x200). (F) Lymphatic vessels at the tumor periphery with open lumina (D2-40, x100).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Morphology of blood and lymphatic vessels in CC. (A) Large vessels (sm-actin (SMA), x100), (B) small vessels (SMA, x200) and (C) microvascular vessels (CD31, x40) in CC. (D) Altered blood vessels with discontinuously hypoplastic smooth muscle cell layer (SMA, x200). (E) Intratumoral compressed lymphatic vessels (D2-40, x200). (F) Lymphatic vessels at the tumor periphery with open lumina (D2-40, x100).
Mentions: To evaluate the histological vascularization pattern of CC we performed immunostaining for the pan-endothelial marker CD31 and smooth muscle marker sm-actin which produced very strong signals in blood vessels of various sizes, that is, large and small vessels as well as microvasculature (Figure 2A-C). The distribution and density of these different sized vessels were analyzed in the tumor center, tumor margin and tumor-free surrounding tissue.Figure 2

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