Skip to main content
Top
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Research article

CD1d- and PJA2-related immune microenvironment differs between invasive breast carcinomas with and without a micropapillary feature

Authors: Naoki Kanomata, Junichi Kurebayashi, Yoshikazu Koike, Rin Yamaguchi, Takuya Moriya

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

Invasive micropapillary carcinoma (IMPC) of the breast is characterized by its unique morphology and frequent nodal metastasis. However, the mechanism for development of this unique subtype has not been clearly elucidated. The aim of this study was to obtain a better understanding of IMPC.

Methods

Using representative cases of mixed IMPC, mRNA expression in the micropapillary area and usual invasive area was compared. Then, immunohistochemical analyses for 294 cases (76 invasive carcinomas with a micropapillary feature [ICMF] and 218 invasive carcinomas without a micropapillary feature [ICNMF]) were conducted. Clinicopathological analyses were also studied.

Results

DNA microarray analyses for mixed IMPC showed that BC-1514 (C21orf118) was commonly upregulated in the micropapillary area. CAMK2N1, CD1d, PJA2, RPL5, SAMD13, TCF4, and TXNIP were commonly downregulated in the micropapillary area. Immunohistochemically, we confirmed that BC-1514 was more upregulated in ICMF than in ICNMF. CD1d and PJA2 were more downregulated in ICMF than ICNMF. All patients with cases of PJA2 overexpression survived without cancer recurrence during the follow-up period, although the differences for disease-free (p = 0.153) or overall survival (p = 0.272) were not significant.

Conclusions

The CD1d- and PJA2-related tumour microenvironment might be crucial for IMPC. Further study of the immune microenvironment and micropapillary features is warranted.
Literature
1.
go back to reference Siriaunkgul S, Tavassoli FA. Invasive micropapillary carcinoma of the breast. Mod Pathol. 1993;6(6):660–2.PubMed Siriaunkgul S, Tavassoli FA. Invasive micropapillary carcinoma of the breast. Mod Pathol. 1993;6(6):660–2.PubMed
2.
go back to reference Luna-More S, Gonzalez B, Acedo C, Rodrigo I, Luna C. Invasive micropapillary carcinoma of the breast. A new special type of invasive mammary carcinoma. Pathol Res Pract. 1994;190(7):668–74.PubMedCrossRef Luna-More S, Gonzalez B, Acedo C, Rodrigo I, Luna C. Invasive micropapillary carcinoma of the breast. A new special type of invasive mammary carcinoma. Pathol Res Pract. 1994;190(7):668–74.PubMedCrossRef
3.
go back to reference Li YS, Kaneko M, Sakamoto DG, Takeshima Y, Inai K. The reversed apical pattern of MUC1 expression is characteristics of invasive micropapillary carcinoma of the breast. Breast Cancer. 2006;13(1):58–63.PubMedCrossRef Li YS, Kaneko M, Sakamoto DG, Takeshima Y, Inai K. The reversed apical pattern of MUC1 expression is characteristics of invasive micropapillary carcinoma of the breast. Breast Cancer. 2006;13(1):58–63.PubMedCrossRef
4.
go back to reference Wei J, Cui L, Liu F, Fan Y, Lang R, Gu F, Guo X, Tang P, Fu L. E-selectin and Sialyl Lewis X expression is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast. Int J Surg Pathol. 2010;18(3):193–200.PubMedCrossRef Wei J, Cui L, Liu F, Fan Y, Lang R, Gu F, Guo X, Tang P, Fu L. E-selectin and Sialyl Lewis X expression is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast. Int J Surg Pathol. 2010;18(3):193–200.PubMedCrossRef
5.
go back to reference Lepe M, Kalife ET, Ou J, Quddus MR, Singh K. Inside-out' p120 immunostaining pattern in invasive micropapillary carcinoma of the breast; additional unequivocal evidence of reversed polarity. Histopathology. 2017;70(5):832–4.PubMedCrossRef Lepe M, Kalife ET, Ou J, Quddus MR, Singh K. Inside-out' p120 immunostaining pattern in invasive micropapillary carcinoma of the breast; additional unequivocal evidence of reversed polarity. Histopathology. 2017;70(5):832–4.PubMedCrossRef
6.
go back to reference Guo X, Fan Y, Lang R, Gu F, Chen L, Cui L, Pringle GA, Zhang X. Fu L. tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast. Mod Pathol. 2008;21(9):1101–7.PubMedCrossRef Guo X, Fan Y, Lang R, Gu F, Chen L, Cui L, Pringle GA, Zhang X. Fu L. tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast. Mod Pathol. 2008;21(9):1101–7.PubMedCrossRef
7.
go back to reference Yamaguchi R, Tanaka M, Kondo K, Yokoyama T, Kaneko Y, Yamaguchi M, Ogata Y, Nakashima O, Kage M, Yano H. Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis. Jpn J Clin Oncol. 2010;40(8):781–7.PubMedCrossRef Yamaguchi R, Tanaka M, Kondo K, Yokoyama T, Kaneko Y, Yamaguchi M, Ogata Y, Nakashima O, Kage M, Yano H. Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis. Jpn J Clin Oncol. 2010;40(8):781–7.PubMedCrossRef
8.
go back to reference Liu F, Lang R, Wei J, Fan Y, Cui L, Gu F, Guo X, Pringle GA, Zhang X, Fu L. Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast. Histopathology. 2009;54(6):741–50.PubMedCrossRef Liu F, Lang R, Wei J, Fan Y, Cui L, Gu F, Guo X, Pringle GA, Zhang X, Fu L. Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast. Histopathology. 2009;54(6):741–50.PubMedCrossRef
9.
go back to reference Ren M, Liu F, Zhu Y, Li Y, Lang R, Fan Y, Gu F, Zhang X. Fu L. absence of caveolin-1 expression in carcinoma-associated fibroblasts of invasive micropapillary carcinoma of the breast predicts poor patient outcome. Virchows Arch. 2014;465(3):291–8.PubMedCrossRef Ren M, Liu F, Zhu Y, Li Y, Lang R, Fan Y, Gu F, Zhang X. Fu L. absence of caveolin-1 expression in carcinoma-associated fibroblasts of invasive micropapillary carcinoma of the breast predicts poor patient outcome. Virchows Arch. 2014;465(3):291–8.PubMedCrossRef
10.
go back to reference Gong Y, Sun X, Huo L, Wiley EL, Rao MS. Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast. Histopathology. 2005;46(1):24–30.PubMedCrossRef Gong Y, Sun X, Huo L, Wiley EL, Rao MS. Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast. Histopathology. 2005;46(1):24–30.PubMedCrossRef
11.
go back to reference Meng F, Liu B, Xie G, Song Y, Zheng X, Qian X, Li S, Jia H, Zhang X, Zhang L, et al. Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast. Breast Cancer Res Treat. 2017;166(2):383–92.PubMedCrossRef Meng F, Liu B, Xie G, Song Y, Zheng X, Qian X, Li S, Jia H, Zhang X, Zhang L, et al. Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast. Breast Cancer Res Treat. 2017;166(2):383–92.PubMedCrossRef
12.
go back to reference Wang XX, Liu BB, Wu X, Su D, Zhu Z. Fu L. loss of leucine zipper putative tumor suppressor 1 (LZTS1) expression contributes to lymph node metastasis of breast invasive micropapillary carcinoma. Pathol Oncol Res. 2015;21(4):1021–6.PubMedPubMedCentralCrossRef Wang XX, Liu BB, Wu X, Su D, Zhu Z. Fu L. loss of leucine zipper putative tumor suppressor 1 (LZTS1) expression contributes to lymph node metastasis of breast invasive micropapillary carcinoma. Pathol Oncol Res. 2015;21(4):1021–6.PubMedPubMedCentralCrossRef
13.
go back to reference Marchio C, Iravani M, Natrajan R, Lambros MB, Savage K, Tamber N, Fenwick K, Mackay A, Senetta R, Di Palma S, et al. Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. J Pathol. 2008;215(4):398–410.PubMedCrossRef Marchio C, Iravani M, Natrajan R, Lambros MB, Savage K, Tamber N, Fenwick K, Mackay A, Senetta R, Di Palma S, et al. Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. J Pathol. 2008;215(4):398–410.PubMedCrossRef
14.
go back to reference Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel M. Tailoring therapies--improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast Cancer 2015. Ann Oncol. 2015;26(8):1533–46.PubMedPubMedCentralCrossRef Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel M. Tailoring therapies--improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast Cancer 2015. Ann Oncol. 2015;26(8):1533–46.PubMedPubMedCentralCrossRef
15.
go back to reference Muller KE, Marotti JD, Memoli VA, Wells WA, Tafe LJ. Impact of the 2013 ASCO/CAP HER2 guideline updates at an Academic Medical Center that performs primary HER2 FISH testing: increase in equivocal results and utility of reflex immunohistochemistry. Am J Clin Pathol. 2015;144(2):247–52.PubMedCrossRef Muller KE, Marotti JD, Memoli VA, Wells WA, Tafe LJ. Impact of the 2013 ASCO/CAP HER2 guideline updates at an Academic Medical Center that performs primary HER2 FISH testing: increase in equivocal results and utility of reflex immunohistochemistry. Am J Clin Pathol. 2015;144(2):247–52.PubMedCrossRef
16.
go back to reference Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, et al. CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science. 1997;278(5343):1626–9.PubMedCrossRef Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, et al. CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science. 1997;278(5343):1626–9.PubMedCrossRef
17.
go back to reference Canchis PW, Bhan AK, Landau SB, Yang L, Balk SP, Blumberg RS. Tissue distribution of the non-polymorphic major histocompatibility complex class I-like molecule. CD1d Immunology. 1993;80(4):561–5.PubMed Canchis PW, Bhan AK, Landau SB, Yang L, Balk SP, Blumberg RS. Tissue distribution of the non-polymorphic major histocompatibility complex class I-like molecule. CD1d Immunology. 1993;80(4):561–5.PubMed
18.
go back to reference Hix LM, Shi YH, Brutkiewicz RR, Stein PL, Wang CR, Zhang M. CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis. PLoS One 2011, 6(6):e20702. Hix LM, Shi YH, Brutkiewicz RR, Stein PL, Wang CR, Zhang M. CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis. PLoS One 2011, 6(6):e20702.
19.
go back to reference Ascierto ML, Idowu MO, Zhao Y, Khalak H, Payne KK, Wang XY, Dumur CI, Bedognetti D, Tomei S, Ascierto PA, et al. Molecular signatures mostly associated with NK cells are predictive of relapse free survival in breast cancer patients. J Transl Med. 2013;11:145.PubMedPubMedCentralCrossRef Ascierto ML, Idowu MO, Zhao Y, Khalak H, Payne KK, Wang XY, Dumur CI, Bedognetti D, Tomei S, Ascierto PA, et al. Molecular signatures mostly associated with NK cells are predictive of relapse free survival in breast cancer patients. J Transl Med. 2013;11:145.PubMedPubMedCentralCrossRef
20.
go back to reference Veldt BJ, van der Vliet HJ, von Blomberg BM, van Vlierberghe H, Gerken G, Nishi N, Hayashi K, Scheper RJ, de Knegt RJ, van den Eertwegh AJ, et al. Randomized placebo controlled phase I/II trial of alpha-galactosylceramide for the treatment of chronic hepatitis C. J Hepatol. 2007;47(3):356–65.PubMedCrossRef Veldt BJ, van der Vliet HJ, von Blomberg BM, van Vlierberghe H, Gerken G, Nishi N, Hayashi K, Scheper RJ, de Knegt RJ, van den Eertwegh AJ, et al. Randomized placebo controlled phase I/II trial of alpha-galactosylceramide for the treatment of chronic hepatitis C. J Hepatol. 2007;47(3):356–65.PubMedCrossRef
21.
go back to reference Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nistico R, Scorziello A, Savoia C, Garbi C, Annunziato L, et al. Control of PKA stability and signalling by the RING ligase praja2. Nat Cell Biol. 2011;13(4):412–22.PubMedCrossRef Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nistico R, Scorziello A, Savoia C, Garbi C, Annunziato L, et al. Control of PKA stability and signalling by the RING ligase praja2. Nat Cell Biol. 2011;13(4):412–22.PubMedCrossRef
22.
go back to reference Zhong J, Wang H, Chen W, Sun Z, Chen J, Xu Y, Weng M, Shi Q, Ma D, Miao C. Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways. Cell Death Dis. 2017;8(5):e2763.PubMedPubMedCentralCrossRef Zhong J, Wang H, Chen W, Sun Z, Chen J, Xu Y, Weng M, Shi Q, Ma D, Miao C. Ubiquitylation of MFHAS1 by the ubiquitin ligase praja2 promotes M1 macrophage polarization by activating JNK and p38 pathways. Cell Death Dis. 2017;8(5):e2763.PubMedPubMedCentralCrossRef
24.
go back to reference Masson D, Zamai M, Tschopp J. Identification of granzyme a isolated from cytotoxic T-lymphocyte-granules as one of the proteases encoded by CTL-specific genes. FEBS Lett. 1986;208(1):84–8.PubMedCrossRef Masson D, Zamai M, Tschopp J. Identification of granzyme a isolated from cytotoxic T-lymphocyte-granules as one of the proteases encoded by CTL-specific genes. FEBS Lett. 1986;208(1):84–8.PubMedCrossRef
25.
go back to reference Legrand F, Driss V, Delbeke M, Loiseau S, Hermann E, Dombrowicz D, Capron M. Human eosinophils exert TNF-alpha and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. J Immunol. 2010;185(12):7443–51.PubMedCrossRef Legrand F, Driss V, Delbeke M, Loiseau S, Hermann E, Dombrowicz D, Capron M. Human eosinophils exert TNF-alpha and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. J Immunol. 2010;185(12):7443–51.PubMedCrossRef
Metadata
Title
CD1d- and PJA2-related immune microenvironment differs between invasive breast carcinomas with and without a micropapillary feature
Authors
Naoki Kanomata
Junichi Kurebayashi
Yoshikazu Koike
Rin Yamaguchi
Takuya Moriya
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5221-9

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine