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Intratumoral Immune Responses Can Distinguish New Primary and True Recurrence Types of Ipsilateral Breast Tumor Recurrences (IBTR).

West NR, Panet-Raymond V, Truong PT, Alexander C, Babinszky S, Milne K, Ross LA, Loken S, Watson PH - Breast Cancer (Auckl) (2011)

Bottom Line: Compared to matched primaries, TRs showed significant trends towards increased CD3(+) and CD8(+) TIL, while these populations were often diminished in NPs.Comparison of IBTRs showed that TRs had significantly higher levels of CD3(+) (P = 0.0136), CD8(+) (P = 0.0092), and CD25(+) (P = 0.0159) TIL than NPs.We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.

View Article: PubMed Central - PubMed

Affiliation: Deeley Research Centre, Vancouver Island Cancer Centre, British Columbia Cancer Agency, 2410 Lee Avenue, Victoria, BC, Canada, V8R 6V5.

ABSTRACT
Ipsilateral breast tumor recurrence (IBTR) is an increasingly common clinical challenge. IBTRs include True Recurrences (TR; persistent disease) and New Primaries (NP; de novo tumors), but discrimination between these is difficult. We assessed tumor infiltrating leukocytes (TIL) as biomarkers for distinguishing these types of IBTR using primary tumors and matched IBTRs from 24 breast cancer patients, half of which were identified as putative TRs and half as NPs using a previously reported clinical algorithm. Intratumoral lymphocyte populations (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) and macrophages (CD68) were quantified by immunohistochemistry in each tumor. Compared to matched primaries, TRs showed significant trends towards increased CD3(+) and CD8(+) TIL, while these populations were often diminished in NPs. Comparison of IBTRs showed that TRs had significantly higher levels of CD3(+) (P = 0.0136), CD8(+) (P = 0.0092), and CD25(+) (P = 0.0159) TIL than NPs. We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.

No MeSH data available.


Related in: MedlinePlus

Illustrative examples of two cases of primary tumors with the corresponding IBTR tumors. Cases were classified as TR IBTR (left) or NP IBTR (right). Panels show H&E, CD8, and CD68 immunohistochemical staining for primary and IBTR tumors in each case (original magnification 10× for H&E and 20× for CD3 and CD68).
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f2-bcbcr-1-2011-105: Illustrative examples of two cases of primary tumors with the corresponding IBTR tumors. Cases were classified as TR IBTR (left) or NP IBTR (right). Panels show H&E, CD8, and CD68 immunohistochemical staining for primary and IBTR tumors in each case (original magnification 10× for H&E and 20× for CD3 and CD68).

Mentions: TIL markers were assessed by immunohistochemistry in the TMA constructed from primary and IBTR tumors for each study subject. Representative examples of immunostaining for CD8 and CD68 in both primary and IBTR lesions are shown for two cases (Fig. 2). Primary and IBTR tumor groups showed no significant differences in mean levels of markers of adaptive (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) or innate (CD68) responses when assessed for the entire cohort (Fig. 3A). Primary and IBTR tumor groups were then reassessed after the latter had been classified by the decision rule clinical algorithm into putative NP or TR type IBTRs. Although not statistically significant, levels of CD3+ and CD8+ TIL tended to be lower in NP lesions compared to NP-associated primaries (Fig. 3B). In contrast, these cells were often more prevalent in TR lesions relative to TR-associated primaries (Fig. 3C). Compared to primary tumors, the median levels of CD8+ TIL were 3.3 fold lower in NP lesions and 2.5 fold higher in TR lesions.


Intratumoral Immune Responses Can Distinguish New Primary and True Recurrence Types of Ipsilateral Breast Tumor Recurrences (IBTR).

West NR, Panet-Raymond V, Truong PT, Alexander C, Babinszky S, Milne K, Ross LA, Loken S, Watson PH - Breast Cancer (Auckl) (2011)

Illustrative examples of two cases of primary tumors with the corresponding IBTR tumors. Cases were classified as TR IBTR (left) or NP IBTR (right). Panels show H&E, CD8, and CD68 immunohistochemical staining for primary and IBTR tumors in each case (original magnification 10× for H&E and 20× for CD3 and CD68).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3117626&req=5

f2-bcbcr-1-2011-105: Illustrative examples of two cases of primary tumors with the corresponding IBTR tumors. Cases were classified as TR IBTR (left) or NP IBTR (right). Panels show H&E, CD8, and CD68 immunohistochemical staining for primary and IBTR tumors in each case (original magnification 10× for H&E and 20× for CD3 and CD68).
Mentions: TIL markers were assessed by immunohistochemistry in the TMA constructed from primary and IBTR tumors for each study subject. Representative examples of immunostaining for CD8 and CD68 in both primary and IBTR lesions are shown for two cases (Fig. 2). Primary and IBTR tumor groups showed no significant differences in mean levels of markers of adaptive (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) or innate (CD68) responses when assessed for the entire cohort (Fig. 3A). Primary and IBTR tumor groups were then reassessed after the latter had been classified by the decision rule clinical algorithm into putative NP or TR type IBTRs. Although not statistically significant, levels of CD3+ and CD8+ TIL tended to be lower in NP lesions compared to NP-associated primaries (Fig. 3B). In contrast, these cells were often more prevalent in TR lesions relative to TR-associated primaries (Fig. 3C). Compared to primary tumors, the median levels of CD8+ TIL were 3.3 fold lower in NP lesions and 2.5 fold higher in TR lesions.

Bottom Line: Compared to matched primaries, TRs showed significant trends towards increased CD3(+) and CD8(+) TIL, while these populations were often diminished in NPs.Comparison of IBTRs showed that TRs had significantly higher levels of CD3(+) (P = 0.0136), CD8(+) (P = 0.0092), and CD25(+) (P = 0.0159) TIL than NPs.We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.

View Article: PubMed Central - PubMed

Affiliation: Deeley Research Centre, Vancouver Island Cancer Centre, British Columbia Cancer Agency, 2410 Lee Avenue, Victoria, BC, Canada, V8R 6V5.

ABSTRACT
Ipsilateral breast tumor recurrence (IBTR) is an increasingly common clinical challenge. IBTRs include True Recurrences (TR; persistent disease) and New Primaries (NP; de novo tumors), but discrimination between these is difficult. We assessed tumor infiltrating leukocytes (TIL) as biomarkers for distinguishing these types of IBTR using primary tumors and matched IBTRs from 24 breast cancer patients, half of which were identified as putative TRs and half as NPs using a previously reported clinical algorithm. Intratumoral lymphocyte populations (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) and macrophages (CD68) were quantified by immunohistochemistry in each tumor. Compared to matched primaries, TRs showed significant trends towards increased CD3(+) and CD8(+) TIL, while these populations were often diminished in NPs. Comparison of IBTRs showed that TRs had significantly higher levels of CD3(+) (P = 0.0136), CD8(+) (P = 0.0092), and CD25(+) (P = 0.0159) TIL than NPs. We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.

No MeSH data available.


Related in: MedlinePlus