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CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.

Koelzer VH, Lugli A, Dawson H, Hädrich M, Berger MD, Borner M, Mallaev M, Galván JA, Amsler J, Schnüriger B, Zlobec I, Inderbitzin D - J Transl Med (2014)

Bottom Line: Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor.Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025).Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO.

View Article: PubMed Central - HTML - PubMed

Affiliation: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr, 31, Bern CH-3010, Switzerland. inti.zlobec@pathology.unibe.ch.

ABSTRACT

Background and aims: Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery.

Methods: Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor.

Results: CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting.

Conclusions: T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.

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Visualization of immune infiltrates in biopsy material and study design. A: Visualization of immune infiltrates and tumor cells by immunohistochemical double-stain for CD8 (upper panel) or CD45RO (lower panel) and pancytokeratin in biopsy material (overview x 50, inset x 300). Stromal infiltrates are indicated by *, arrows indicate intraepithelial CD8+ or CD45RO+ T-cells. B: Study Design. 346 CRC patients were entered into the study, 185 of which had matched biopsies. Histopathological features and clinical data were re-reviewed. Immunohistochemistry for pancytokeratin and CD8 or CD45RO was performed. CD8+ and CD45RO+ T-cell infiltrates in biopsy specimens were evaluated in five HPF each of stroma and neoplastic epithelium. T-cell infiltrates were analysed for prediction of patient survival and histopathologic features of the matched resection specimen.
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Figure 1: Visualization of immune infiltrates in biopsy material and study design. A: Visualization of immune infiltrates and tumor cells by immunohistochemical double-stain for CD8 (upper panel) or CD45RO (lower panel) and pancytokeratin in biopsy material (overview x 50, inset x 300). Stromal infiltrates are indicated by *, arrows indicate intraepithelial CD8+ or CD45RO+ T-cells. B: Study Design. 346 CRC patients were entered into the study, 185 of which had matched biopsies. Histopathological features and clinical data were re-reviewed. Immunohistochemistry for pancytokeratin and CD8 or CD45RO was performed. CD8+ and CD45RO+ T-cell infiltrates in biopsy specimens were evaluated in five HPF each of stroma and neoplastic epithelium. T-cell infiltrates were analysed for prediction of patient survival and histopathologic features of the matched resection specimen.

Mentions: All biopsies from a single patient were first scanned at low-power magnification (10x) and the five densest regions of intratumoral (i) and stromal (s) CD8+ and CD45RO+ T-cells were identified (Figure 1A). Within these areas, CD8i, CD8s, CD45ROi, and CD45ROs T-cells were then counted in 5 high-power fields each (HPF; 40x; area 0.1886 mm2). The average number of infiltrating T-cells per HPF was determined for each area and used for statistical analysis.


CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.

Koelzer VH, Lugli A, Dawson H, Hädrich M, Berger MD, Borner M, Mallaev M, Galván JA, Amsler J, Schnüriger B, Zlobec I, Inderbitzin D - J Transl Med (2014)

Visualization of immune infiltrates in biopsy material and study design. A: Visualization of immune infiltrates and tumor cells by immunohistochemical double-stain for CD8 (upper panel) or CD45RO (lower panel) and pancytokeratin in biopsy material (overview x 50, inset x 300). Stromal infiltrates are indicated by *, arrows indicate intraepithelial CD8+ or CD45RO+ T-cells. B: Study Design. 346 CRC patients were entered into the study, 185 of which had matched biopsies. Histopathological features and clinical data were re-reviewed. Immunohistochemistry for pancytokeratin and CD8 or CD45RO was performed. CD8+ and CD45RO+ T-cell infiltrates in biopsy specimens were evaluated in five HPF each of stroma and neoplastic epithelium. T-cell infiltrates were analysed for prediction of patient survival and histopathologic features of the matched resection specimen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4022053&req=5

Figure 1: Visualization of immune infiltrates in biopsy material and study design. A: Visualization of immune infiltrates and tumor cells by immunohistochemical double-stain for CD8 (upper panel) or CD45RO (lower panel) and pancytokeratin in biopsy material (overview x 50, inset x 300). Stromal infiltrates are indicated by *, arrows indicate intraepithelial CD8+ or CD45RO+ T-cells. B: Study Design. 346 CRC patients were entered into the study, 185 of which had matched biopsies. Histopathological features and clinical data were re-reviewed. Immunohistochemistry for pancytokeratin and CD8 or CD45RO was performed. CD8+ and CD45RO+ T-cell infiltrates in biopsy specimens were evaluated in five HPF each of stroma and neoplastic epithelium. T-cell infiltrates were analysed for prediction of patient survival and histopathologic features of the matched resection specimen.
Mentions: All biopsies from a single patient were first scanned at low-power magnification (10x) and the five densest regions of intratumoral (i) and stromal (s) CD8+ and CD45RO+ T-cells were identified (Figure 1A). Within these areas, CD8i, CD8s, CD45ROi, and CD45ROs T-cells were then counted in 5 high-power fields each (HPF; 40x; area 0.1886 mm2). The average number of infiltrating T-cells per HPF was determined for each area and used for statistical analysis.

Bottom Line: Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor.Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025).Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO.

View Article: PubMed Central - HTML - PubMed

Affiliation: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstr, 31, Bern CH-3010, Switzerland. inti.zlobec@pathology.unibe.ch.

ABSTRACT

Background and aims: Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery.

Methods: Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor.

Results: CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting.

Conclusions: T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.

Show MeSH
Related in: MedlinePlus