Role of undifferentiation markers and androgen receptor expression in triple‐negative breast cancer

Castañeda, Carlos A.; Castillo, Miluska; Enciso, Javier; Enciso, Nathaly; Bernabe, Luis A.; Sanchez, Joselyn; Guerra, Henry; Chavez, Carlos M.; Landa-Baella, Maria; De-La-Cruz, Miguel; Villa-Robles, Maria R.; Tello, Katherine; Gómez, Henry L.

doi:10.1111/tbj.13464

Cited by 4 publications

(6 citation statements)

References 8 publications

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“…Whereas, mean CD3 was significantly lower in AR− versus AR+ (80.7% versus 93.3%, respectively, p = 0.007). On the other side, previous publications reported that CD8+ were more frequent in AR+ than AR− tumours [ 12 , 29 , 30 ], in contrast to our study which showed that neither CD8 nor CD4 were statistically different between AR+ and AR− tumours.…”

Section: Discussioncontrasting

confidence: 99%

“…It is well established that the expression of AR differs according to molecular subtypes of BC with more frequent expression in ER negative cancers. The prevalence of AR+ expressing tumours is generally ranging from 10% to 41% in TNBC cases [1,[8][9][10][11][12][13][14], with rare reports showing rates up to 79% [15,16]. In accordance with most published reports, our rate of AR expression in TNBC was 21.2%.…”

Section: Discussionsupporting

confidence: 89%

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Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer

Elghazawy¹,

Bakkach²,

Helal³

et al. 2021

ecancer

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Background Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumour-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behaviour is still not fully understood. Methods Thirty-six TNBC patients were evaluated for AR (positive if ≥1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as <50%. Results The mean age was 52.5 years and 27.8% were ≥60 years. Seven patients (21.2%) were AR+. All AR+ cases were postmenopausal (≥50 years old). LPBC was 32.2% of the whole cohort. Median TILs were 37.5% and 10% ( p = 0.1) and median CD20 was 20% and 7.5% ( p = 0.008) in AR− and AR+, respectively. Mean CD3 was 80.7% and 93.3% ( p = 0.007) and CD8 was 75% and 80.8% ( p = 0.41) in AR− and AR+, respectively. All patients who were ≥60 years old expressed CD20. LDBC was found to be significantly higher in N+ versus N− patients ( p = 0.03) with median TILs of 20% versus 50% in N+ versus N−, respectively ( p = 0.03). LDBC was associated with higher risk of lymph node (LN) involvement (odds ratio = 6; 95% CI = 1.05–34.21; p = 0.04). Conclusions AR expression was evident in older age (≥50 years). Median CD20 was higher in AR− TNBC, while mean CD3 was higher in AR+ tumours. LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 89%

Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer

Elghazawy¹,

Bakkach²,

Helal³

et al. 2021

ecancer

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“…This notion may have clinical relevance suggesting that already established neuroendocrine serum markers such as chromogranin A and neuron‐specific enolase as covering different resistance mechanisms might be well combined with ALCAM for the prediction of ENZA and ABI treatment 15 . On the other hand, the correlation of ALCAM expression with AR gene expression score seems to be in line with current observations made in triple negative breast cancer where high ALCAM tissue protein expressions were shown to be associated with higher AR protein expression 48 . However, in our experiment ALCAM knock‐down did not consistently influenced the expression of AR regulated genes, suggesting that ALCAM is coregulated with these genes rather than being their regulator.…”

Section: Discussionsupporting

confidence: 86%

Proteome profiling of enzalutamide‐resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration‐resistant prostate cancer

Csizmarik

Keresztes

Nagy

et al. 2022

Intl Journal of Cancer

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Enzalutamide (ENZA) is a frequently used therapy in metastatic castration‐resistant prostate cancer (mCRPC). Baseline or acquired resistance to ENZA have been observed, but the molecular mechanisms of resistance are poorly understood. We aimed to identify proteins involved in ENZA resistance and to find therapy‐predictive serum markers. We performed comparative proteome analyses on ENZA‐sensitive parental (LAPC4, DuCaP) and ‐resistant prostate cancer cell lines (LAPC4‐ENZA, DuCaP‐ENZA) using liquid chromatography tandem mass spectrometry (LC‐MS/MS). The top four most promising candidate markers were selected using bioinformatic approaches. Serum concentrations of selected markers (ALCAM, AGR2, NDRG1, IDH1) were measured in pretreatment samples of 72 ENZA‐treated mCRPC patients using ELISA. In addition, ALCAM serum levels were measured in 101 Abiraterone (ABI) and 100 Docetaxel (DOC)‐treated mCRPC patients' baseline samples. Results were correlated with clinical and follow‐up data. The functional role of ALCAM in ENZA resistance was assessed in vitro using siRNA. Our proteome analyses revealed 731 significantly differentially abundant proteins between ENZA‐sensitive and ‐resistant cells and our filtering methods identified four biomarker candidates. Serum analyses of these proteins revealed only ALCAM to be associated with poor patient survival. Furthermore, higher baseline ALCAM levels were associated with poor survival in ABI‐ but not in DOC‐treated patients. In LAPC4‐ENZA resistant cells, ALCAM silencing by siRNA knockdown resulted in significantly enhanced ENZA sensitivity. Our analyses revealed that ALCAM serum levels may help to identify ENZA‐ and ABI‐resistant patients and may thereby help to optimize future clinical decision‐making. Our functional analyses suggest the possible involvement of ALCAM in ENZA resistance.

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“…Whereas, mean CD3 was signi cantly lower in AR-vs. AR+ (80.7% vs 93.3% respectively, p = 0.007). Previous publications reported that CD8 + were more frequent in AR + than ARtumors 11,27,28 . In contrast, neither CD8 nor CD4 were statistically different between AR + and AR-tumors, in our study.…”

Section: Discussionmentioning

confidence: 77%

Clinico-pathological relationship between androgen receptor (AR) and tumor infiltrating lymphocytes (TILs) in triple negative breast cancer (TNBC)

Elghazawy

Bakkach

Helal

et al. 2021

Preprint

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Background Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumor-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behavior is still not fully understood. Methods Thirty-six TNBC patients were evaluated for AR (positive if ≥ 1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as having stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as < 50%. Results The mean age was 52.5 years and 27.8% were ≥ 60 years. Seven patients (21.2%) were AR+. All AR + cases were postmenopausal (≥ 50 years old). No statistical difference was found in median overall survival (OS) between AR- and AR + groups (31.5 vs. 25 months, p = 0.77). LPBC was 32.2%. Median TILs was 37.5% and 10% (p = 0.1) and median CD20 was 20% and 7.5% (p = 0.008) in AR- and AR+, respectively. Mean CD3 was 80.7% and 93.3% (p = 0.007) and CD8 was 75% and 80.8% (p = 0.41) in AR- and AR + respectively. All patients who were ≥ 60 years old expressed CD20. LDBC was found to be significantly higher in N + vs. N- patients (p = 0.03) with median TILs of 20% vs. 50% in N + vs. N-, respectively (p = 0.03). LDBC was associated with higher risk of lymph node involvement (OR = 6, 95% CI = 1.05–34.21, p = 0.04). Conclusions AR expression was evident in older age (≥ 50 years). Median CD20 was higher in AR- TNBC, while mean CD3 was higher in AR + tumors. LDBC was associated with higher risk of lymph node involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.

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Role of undifferentiation markers and androgen receptor expression in triple‐negative breast cancer

Cited by 4 publications

References 8 publications

Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer

Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer

Proteome profiling of enzalutamide‐resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration‐resistant prostate cancer

Clinico-pathological relationship between androgen receptor (AR) and tumor infiltrating lymphocytes (TILs) in triple negative breast cancer (TNBC)

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