Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes

Abstract Background: Melanoma brain metastases are the main cause of specific death among patients with metastatic melanoma. The biology of melanoma brain metastases remains largely to be deciphered, as there have been only a few genomic studies on brain metastatic samples. In this study, melanoma metastatic lymph nodes were used with the aim to identify biomarkers associated with the occurrence of brain metastases. Methods: Fifty-one patients with melanoma lymph node metastasis and a median follow-up of 48 months were included in the development cohort. Transcriptomic data were obtained from these metastatic lymph nodes and patients who developed brain metastases and those who did not were compared. Recommendations for tumour marker prognostic studies (REMARK recommendations) were followed.Results: From transcriptomic data, we identified PROM2 which was significantly overexpressed in metastatic lymph nodes of patients who developed brain metastases compared to those who did not. Using immunohistochemistry with two different anti-PROM2 antibodies, a PROM2 score was developed for metastatic lymph nodes. Using a cut-off of 5, a PROM2 mean score ≥5 was significantly associated with an increased risk of brain metastases and an increased hazard risk of death by 4.These results were confirmed in an internal validation cohort of 50 additional patients with melanoma lymph node metastases.Conclusions: In this study, we identified PROM2 expression as a biomarker predictive of the occurrence of distant metastases, particularly brain metastases, among patients with stage III melanoma. Our findings open new perspectives to validate PROM2 as a useful biomarker for clinical trials in the adjuvant setting, and as a potential biotarget for the treatment of metastatic melanoma.

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Increased risk of brain metastases among patients with melanoma and PROM2 expression in metastatic lymph nodes

Clinical and Translational Medicine ◽

10.1002/ctm2.198 ◽

2020 ◽

Vol 10 (8) ◽

Author(s):

Thuy Thi Nguyen ◽

Guillaume Gapihan ◽

Pauline Tetu ◽

Frédéric Pamoukdjian ◽

Morad El Bouchtaoui ◽

...

Keyword(s):

Brain Metastases ◽

Lymph Nodes ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph ◽

Increased Risk

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Ezrin expression in primary breast cancer, metastatic lymph nodes and normal breast tissue

Geburtshilfe und Frauenheilkunde ◽

10.1055/s-0030-1254964 ◽

2010 ◽

Vol 70 (05) ◽

Author(s):

D Gschwantler-Kaulich ◽

C Natter ◽

S Steurer ◽

I Walter ◽

C Singer

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph ◽

Ezrin Expression

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Would clipping and removal of all ultrasound abnormal metastatic lymph nodes predict nodal response in breast cancer patients with neoadjuvant chemotherapy?

The Breast ◽

10.1016/s0960-9776(21)00231-9 ◽

2021 ◽

Vol 56 ◽

pp. S75

Author(s):

G.H. Lim ◽

M. Gudi ◽

S.Y. Teo ◽

R.P. Ng ◽

Y.S. Lee ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Lymph Nodes ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph

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Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer

Cancers ◽

10.3390/cancers13225616 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5616

Author(s):

Eugenia Fernandez ◽

Luis Ubillos ◽

Nabila Elgul ◽

María Florencia Festari ◽

Daniel Mazal ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Cancer Biology ◽

Molecular Mechanisms ◽

Health Concern ◽

Breast Cancer Cell Lines ◽

Prognostic Impact ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph

Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.

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Clinical Significance of Subtype Classification in Metastatic Lymph Nodes of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

The International Journal of Biological Markers ◽

10.5301/jbm.5000128 ◽

2015 ◽

Vol 30 (2) ◽

pp. 174-183 ◽

Cited By ~ 1

Author(s):

Noriko Nemoto ◽

Yukiko Shibahara ◽

Hiroshi Tada ◽

Keiko Uchida ◽

Keely M. McNamara ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Lymph Nodes ◽

Cancer Patients ◽

Clinical Outcomes ◽

Primary Tumor ◽

Breast Cancer Patients ◽

Ki 67 ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph

Background Neoadjuvant chemotherapy has been increasingly utilized in the treatment of breast cancer patients. However, there are no established surrogate markers predicting the response to subsequent adjuvant therapy and clinical outcome of patients. In particular, whether primary or lymph nodes metastasis should be evaluated for these analyses has remained unknown. Therefore, in this study, we first evaluated the differences in biomarkers between primary and metastatic cancer tissues in the patients undergoing neoadjuvant chemotherapy. We then correlated the findings with the clinical outcomes of these patients. Methods We examined 49 patients receiving neoadjuvant chemotherapy and subsequent surgery with lymph node metastasis. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki-67 were all immunohistochemically evaluated in core needle biopsy samples from primary and metastatic tumors following chemotherapy. Results No statistically significant differences in these markers were detected between the primary tumor and metastatic lymph nodes following therapy, but the Ki-67 labeling index was significantly higher in metastatic lymph nodes than in primary tumor (p = 0.017). The patients associated with luminal A type carcinoma in their lymph nodes following chemotherapy demonstrated significantly better clinical outcomes (disease-free survival: p = 0.0045, overall survival: p = 0.0006) than those who were not. Conclusion These data indicate that subtype classification following chemotherapy, in the metastatic lymph nodes rather than primary tumor could predict long-term outcomes of patients undergoing neoadjuvant chemotherapy.

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