scholarly journals Tumor budding as a prognostic criterion of colorectal cancer

Pathologia ◽  
2021 ◽  
Vol 18 (3) ◽  
pp. 346-351
Author(s):  
I. I. Yakovtsova ◽  
V. M. Cheverda ◽  
O. V. Dolhaia ◽  
A. S. Yakymenko ◽  
I. V. Ivakhno
Keyword(s):  
Colorectal Cancer ◽  
Malignant Tumors ◽  
Fatal Outcome ◽  
Tumor Budding ◽  
Lethal Outcome ◽  
Regional Lymph Nodes ◽  
Prognostic Features ◽  
Group I ◽  
Prognostic Criterion ◽  
The Moment

Colorectal cancer (CRC) is the second leading cause of mortality among cancers after malignant tumors of respiratory system. One of the most significant prognostic features of CRC is tumor budding (TB), which isn’t widely implemented in clinical practice. The aim of this research: to find the prognostic criteria of recurrence and lethal outcome of CRR IIA and IIIB stages (рТ3N0-2M0), the ratio of tumors with certain differentiation in groups of research was taken equal. Material and methods. The group I was formed from primary CRC without recurrences. The main relapse-free survival time was 5 years (62.5 ± 16.5 months). The ІІ group – primary CRC with recurrences; ІІА – with recurrences during 5 years from the moment when the tumor was removed, without fatal outcome; ІІВ – with recurrences and lethal outcome from genera­lization of tumor process during 5 years from the moment when the tumor was removed. The microslides of CRC were made by using the standard methods. Results. TB was identified in 46.66 % (28/60) of CRC рТ3N0-2M0. The direct relationship between tumor grade and presence of TB was found (Р < 0.05), but TB didn’t define differentiation of the CRC. There was a statistically significant relationship between TB and metastatic spreading of CRC to regional lymph nodes (Р < 0.001). Metastasis was associated with 3 stage of TB, absence of metastasis was typical for CRC without TB. The tendency was found in a larger number of cases of the CRC with TB 3 stage among recurring CRC compared with CRC without recurrence, mainly due to the ІІВ group of the research. Inverse correlation between TB stage and time of recurrence appearance was found (Р < 0.05). TB in central tumor sites was followed by presence and higher stage of TB in peripheral tumor sites (Р < 0.05), that can be taken into account during biopsies of CRC. Conclusions. TB is a prognostic criterion of metastasis and time of recurrence appearance for CRC рТ3N0-2M0, which is mostly typical for tumors in patients with recurrences and lethal outcome at the taken equal ratio of tumors by differen­tiation.

Morphological features and criteria of prognosis for stromal component of colorectal cancer ІІА-ІІІВ stages

2021 ◽  
Vol 43 (3-4) ◽  
pp. 74-78
Author(s):  
I. I. Yakovtsova ◽  
◽  
A. S. Yakimenko ◽  
I. V. Ivakhno ◽  
◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatal Outcome ◽  
Disease Free Survival ◽  
Morphological Features ◽  
Free Survival ◽  
Prognostic Features ◽  
Prognostic Criteria ◽  
Group I ◽  
Stromal Component ◽  
Disease Free

Colorectal cancer (CRC) is the second leading cause of mortality among cancers after tumors of the respiratory system. One of the most significant prognostic criteria of CRC are the features of stromal component, which are not implemented in clinical practice. The aim was to study the main morphological features of the stroma of CRC T3N0-2M0 and to search for prognostic criteria of their recurrence and death. Group I included primary CRC without recurrences. Group II – primary CRC with recurrences; IIA – with recurrences that did not lead to death; ІІВ – with recurrences and fatal outcome from generalization of tumor process during 5 years from lethal outcome from the moment when the tumor was removed. The microslides of CRC were made by using the standard methods with G + E staining; immunohistochemical (IHC) reaction was performed by using monoclonal antibodies to smooth muscle actin alpha and vimentin. CRC with a stromal-parenchymal ratio (SPR)>50% were in 43.3% (26/60) of cases. SPR>50% is a prognostic criterion for recurrence (p<0.05), shorter disease free survival (p<0.001) and metastasis to regional lymph nodes (p<0.001). Immature stroma type of CRC IIA-IIIB stages is associated with the presence of tumor budding (p<0.001), G3 differentiation (p<0.01), shorter disease-free survival (p<0.001), metastatic activity (p<0.05); among recurrent CRC, the immature type of stroma is associated with the death of patients (p<0.05). A diffuse presence of tumor-activated fibroblasts is one of the criteria for immature CRC stroma (p<0.003), however, as an independent prognostic feature, it has limited prognostic value. SPR>50% and immature type of stroma are prognostic features for recurrence, metastasis and term of recurrence for CRC pT3N0-2M0; the presence of an immature type of stroma was associated with patient death.

scholarly journals The role of tumoral stroma in determining the forecast of recurrence and fatal consequence of stage IIA-IIIB colorectal cancer

2021 ◽  
pp. 13-15
Author(s):  
Alina Yakimenko
Keyword(s):  
Colorectal Cancer ◽  
Smooth Muscle Actin ◽  
Tumor Stroma ◽  
Malignant Neoplasms ◽  
Recurrence Free Survival ◽  
Lethal Outcome ◽  
Free Survival ◽  
Prognostic Criteria ◽  
Group I ◽  
Prognostic Criterion

Colorectal cancer (CRC) ranks 2nd in the structure of mortality from malignant neoplasms (MN). One of the criteria for the prognosis of CRC may be a tumor stroma, which has not been widely used in clinical practice. The aim was to determine the main morphological features of the stroma CRC T3N0-2M0 and search for prognostic criteria for their recurrence and lethal outcome according to the operating material and autopsy. Materials and methods. Group I included primary CRC without recurrence. The average recurrence-free period was 5 years (62.5±16.5 months). Group II – primary CRC with recurrence; IIA – with recurrences within 5 years from the date of tumor removal that did not lead to death; IIB – with the appearance of recurrence and lethal consequence of the generalization of the tumor process within 5 years from the moment of removal of the primary tumor. CRC micropreparations made according to the standard method with G + E staining were studied; immunohistochemical study was performed using monoclonal antibodies to smooth muscle actin alpha. Results. Stromal-parenchymal ratio >50 % is a prognostic criterion for recurrence (p<0.05) and shorter recurrence-free survival (p<0.001) of patients with stage IIA-IIIB CRC. Immature stroma type CRC stage IIA-IIIB is associated with the presence of tumor budding (p<0.001), G3 differentiation (p<0.01), shorter recurrence-free survival (p<0.001); among recurrent CRCs, the immature type of stroma is associated with the lethal outcome of patients (p<0.05). Expressed levels of tumor-activated fibroblasts are one of the criteria for immature CRC stroma (p<0.003), but as an independent prognostic criterion has limited prognostic value. Conclusions. TSR and immature type of stroma are prognostic criteria for recurrence and recurrence period of CRC pT3N0-2M0, more typical of tumors of patients with recurrence and lethal outcome with the same ratio of tumors by differentiation.

scholarly journals Membranous S100A10 Involvement in the Tumor Budding of Colorectal Cancer During Oncogenesis: Report of Two Cases with Immunohistochemical Analysis

2020 ◽  
Author(s):  
Kazumori Arai ◽  
Hisato Ishimatsu ◽  
Tomohiro Iwasaki ◽  
Chinatsu Tsuchiya ◽  
Akihiro Sonoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
S100 Protein ◽  
Immunohistochemical Analysis ◽  
Tumor Budding ◽  
Plasminogen Activation ◽  
Cell Dynamics ◽  
Regional Lymph Nodes ◽  
Mesenchymal Transition

Abstract Background: Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial–mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Case presentation: In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, giving rise to TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders. Conclusions: During oncogenesis, membranous S100A10 has the potential to be related to TB of CRC. This may be due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.

scholarly journals Membranous S100A10 involvement in the tumor budding of colorectal cancer during oncogenesis: report of two cases with immunohistochemical analysis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Kazumori Arai ◽  
Hisato Ishimatsu ◽  
Tomohiro Iwasaki ◽  
Chinatsu Tsuchiya ◽  
Akihiro Sonoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
S100 Protein ◽  
Immunohistochemical Analysis ◽  
Tumor Budding ◽  
Plasminogen Activation ◽  
Cell Dynamics ◽  
Regional Lymph Nodes ◽  
Mesenchymal Transition

Abstract Background Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial-mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Case presentation In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, giving rise to TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders. Conclusions During oncogenesis, membranous S100A10 has the potential to be related to TB of CRC. This may be due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.

scholarly journals RISK FACTORS OF DEVELOPMENT OF LETAL OUTCOME WITH THE DEFEAT OF THE RESPIRATORY SYSTEM IN HIV-INFECTED PATIENTS

2019 ◽  
Vol 24 (4) ◽  
pp. 172-177
Author(s):  
Daria D. Arutyunova ◽  
A. N. Gerasimov ◽  
M. N. Allenov ◽  
N. V. Maloletneva ◽  
O. Yu. Shabalina ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hiv Infection ◽  
Fibrinogen Level ◽  
Fatal Outcome ◽  
Multivariate Models ◽  
Mathematical Methods ◽  
Lethal Outcome ◽  
Mortality Probability ◽  
The Moment ◽  
High Level

Tuberculosis remains the leading cause of death in HIV patients. The purpose of our study is to assess risk factors of the fatal outcome development in HIV infection patients with tuberculosis using mathematical methods. A retrospective analysis of lethal cases was performed using statistical methods and multivariate models of the mortality probability in 113 HIV infection patients at the stage of secondary diseases with respiratory damage were calculated. While calculating the prognosis coefficients of the lethal outcome was established the higher the fibrinogen level at the moment of hospitalization is the better the patients’ prognosis, and the high level of other indicators increases the probability of the lethal outcome.

scholarly journals Membranous S100A10 Involvement in the Tumor Budding of Colorectal Cancer During Oncogenesis: Report of Two Cases with Immunohistochemical Analysis

2020 ◽  
Author(s):  
Kazumori Arai ◽  
Hisato Ishimatsu ◽  
Tomohiro Iwasaki ◽  
Chinatsu Tsuchiya ◽  
Akihiro Sonoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
S100 Protein ◽  
Immunohistochemical Analysis ◽  
Tumor Budding ◽  
Plasminogen Activation ◽  
Cell Dynamics ◽  
Regional Lymph Nodes ◽  
Mesenchymal Transition

Abstract Background Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial–mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Recently, the involvement of S100A10 in EMT has been reported. Furthermore, a recent study suggested that S100A10 and ANX A2 are related to the budding of a special type of CRC cells.Case presentation In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, which originates from TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders.Conclusions Membranous S100A10 is related to the TB of CRC during oncogenesis. This is possibly due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.

scholarly journals RISK FACTORS OF DEVELOPMENT OF LETAL OUTCOME WITH THE DEFEAT OF THE RESPIRATORY SYSTEM IN HIV-INFECTED PATIENTS

2019 ◽  
Vol 24 (4) ◽  
pp. 172-177
Author(s):  
Daria D. Arutyunova ◽  
A. N. Gerasimov ◽  
M. N. Allenov ◽  
N. V. Maloletneva ◽  
O. Yu. Shabalina ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hiv Infection ◽  
Fibrinogen Level ◽  
Fatal Outcome ◽  
Multivariate Models ◽  
Mathematical Methods ◽  
Lethal Outcome ◽  
Mortality Probability ◽  
The Moment ◽  
High Level

Tuberculosis remains the leading cause of death in HIV patients. The purpose of our study is to assess risk factors of the fatal outcome development in HIV infection patients with tuberculosis using mathematical methods. A retrospective analysis of lethal cases was performed using statistical methods and multivariate models of the mortality probability in 113 HIV infection patients at the stage of secondary diseases with respiratory damage were calculated. While calculating the prognosis coefficients of the lethal outcome was established the higher the fibrinogen level at the moment of hospitalization is the better the patients’ prognosis, and the high level of other indicators increases the probability of the lethal outcome.

Causes and outcomes of hospitalizations among people living with HIV in Georgia’s referral institution, 2012–2017

2021 ◽  
Vol 32 (7) ◽  
pp. 662-670
Author(s):  
Nino Rukhadze ◽  
Ole Kirk ◽  
Nikoloz Chkhartishvili ◽  
Natalia Bolokadze ◽  
Lali Sharvadze ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Immunology ◽  
Fatal Outcome ◽  
Cd4 Count ◽  
People Living With Hiv ◽  
Lethal Outcome ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Living With Hiv ◽  
Cd4 Cell

We assessed trends in causes and outcomes of hospitalization among people living with HIV (PLWH) admitted to the Infectious Diseases, AIDS and Clinical Immunology Research Center (IDACIRC) in Tbilisi, Georgia. Retrospective analysis included adult PLWH admitted to IDACIRC for at least 24 h. Internationally validated categorization was used to split AIDS admissions into mild, moderate, and severe AIDS. A total of 2085 hospitalizations among 1123 PLWH were registered over 2012–2017 with 65.1% (731/1123) of patients presenting with CD4 count <200. Of 2085 hospitalizations, 931 (44.7%) were due to AIDS-defining illnesses. In 2012, AIDS conditions accounted for 50.3% of admissions compared to 41.6% in 2017 ( p = 0.16). Overall, 167 hospitalizations (8.0%) resulted in lethal outcome. AIDS admissions had higher mortality than non-AIDS admissions (11.5% vs 5.2%, p < 0.0001). Among 167 deceased patients, 137 (82.0%) had CD4 count <200 at admission. In multivariate analysis, factors significantly associated with mortality included severe AIDS versus non-AIDS admission (OR 2.81, 95% CI: 1.10–7.15), CD4 cell counts <50 (OR 4.34, 95% CI: 2.52–7.47), and 50–100 (OR 2.37, 95% CI: 1.27–4.42) versus >200. Active AIDS disease remains a significant cause of hospitalization and fatal outcome in Georgia. Earlier diagnosis of HIV is critical for decreasing AIDS hospitalizations and mortality.

scholarly journals The Relationship Between Tumor Budding, Tumor Microenvironment, and Survival in Patients with Primary Operable Colorectal Cancer

2019 ◽  
Vol 26 (13) ◽  
pp. 4397-4404 ◽  
Author(s):  
Hester C. van Wyk ◽  
Antonia Roseweir ◽  
Peter Alexander ◽  
James H. Park ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Evaluation Method ◽  
Venous Invasion ◽  
Staging System ◽  
Consensus Conference ◽  
Tumor Budding ◽  
Inflammatory Cell Infiltrate ◽  
Cancer Specific Survival ◽  
The Relationship

Abstract Background Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for primary operable CRC.

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