Differential expression of immunohistochemical markers in primary lung and breast cancers enriched for triple‐negative tumours

Provenzano, Elena; Byrne, David; Russell, Prudence A.; Wright, Gavin; Generali, Daniele; Fox, Stephen B.

doi:10.1111/his.12765

Cited by 20 publications

(20 citation statements)

References 57 publications

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“…NKX2-1 is a transcription factor that regulates thyroid-specific genes and genes involved in morphogenesis. NKX2-1 has previously been identified as a marker to distinguish breast cancer from other types of cancer 48 . DNASE1, CASP3 and PPT1 are involved in cell death by apoptosis [49][50][51] .…”

Section: Resultsmentioning

confidence: 99%

DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer

Beetch

Harandi-Zadeh

Yang

et al. 2020

Sci Rep

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triple-negative breast cancer (tnBc) is a subtype of breast cancer unresponsive to traditional receptortargeted treatments, leading to a disproportionate number of deaths. invasive breast cancer is believed to evolve from non-invasive ductal carcinoma in situ (DciS). Detection of triple-negative DciS (tn-DciS) is challenging, therefore strategies to study molecular events governing progression of pre-invasive tn-DciS to invasive tnBc are needed. Here, we study a canine tn-DciS progression and investigate the DnA methylation landscape of normal breast tissue, atypical ductal hyperplasia (ADH), DciS and invasive breast cancer. We report hypo-and hypermethylation of genes within functional categories related to cancer such as transcriptional regulation, apoptosis, signal transduction, and cell migration. DnA methylation changes associated with cancer-related genes become more pronounced at invasive breast cancer stage. Importantly, we identify invasive-only and DCIS-specific DNA methylation alterations that could potentially determine which lesions progress to invasive cancer and which could remain as pre-invasive DciS. changes in DnA methylation during tn-DciS progression in this canine model correspond with gene expression patterns in human breast tissues. this study provides evidence for utilizing methylation status of gene candidates to define late-stage (DCIS and invasive), invasive stage only or DciS stage only of tn-DciS progression. Breast cancer is classified into subtypes based on the expression of growth factor receptors including the estrogen receptor (ER), the progesterone receptor (PR), and the receptor for human epidermal growth factor (HER-2) 1. Growth of breast tumors expressing any of these receptors may be controlled effectively by treatment in the adjuvant setting with receptor-targeted drugs 2. However, breast tumors that do not express any of these receptors have no known effective adjuvant treatment capable of controlling tumor growth. Such tumors are referred to as triple-negative breast cancers (TNBC) and are the most aggressive and lethal of all breast malignancies 2. TNBC accounts for 15% of breast cancer cases and a disproportionate percentage of breast cancer deaths among women 3. It has been shown that patients with TNBC have poor prognosis and shorter median time to relapse compared to patients with other subtypes of breast cancer 4. Ductal carcinoma in situ (DCIS) is defined as a non-invasive overgrowth of cells characterized by high proliferation within the breast ductal system. Studies suggest that triple-negative DCIS (TN-DCIS), a rare type of DCIS, is a precursor stage of invasive breast cancer 5,6. Therefore, early detection of TN-DCIS is important in preventing breast cancer cases that may progress to triple negative invasive carcinoma. However, TN-DCIS is challenging to detect at early stage in humans 7. Despite efforts to use immunohistochemistry to measure receptor expression in scientific studies of human DCIS tissues, detection of receptor status, including ER, is not routi...

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Section: Resultsmentioning

confidence: 99%

DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer

Beetch

Harandi-Zadeh

Yang

et al. 2020

Sci Rep

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“…30 On the basis of the fact that the majority of breast cancers express ER and a low proportion of lung cancer specimens are positive for ER, it has been suggested that ER should be included in a differential diagnostic panel. 21 However, caution is warranted, as interpretation of ER positivity alone may lead to the false assumption of a pulmonary breast cancer metastasis, 2,18,31 specifically because of the high sensitivity of SP1, the ER clone used in this study. 32 Controversial observations have been made regarding survival, as some authors have reported a favourable outcome in patients with ER-positive tumours, 23,33,34 whereas others could not find a statistically significant difference.…”

Section: Discussionmentioning

confidence: 97%

“…Staining characteristics for thyroid transcription factor-1 (TTF-1), napsin-A, cytokeratin (CK) 5/6, and p40 Studies on NSCLC tissue specimens found ER positivity in 0-73%. [18][19][20][21][22][23] Some of this great variability may be explained by the use of different clones, 24 and the definition of positivity in tumours with cytoplasmic reactivity in some studies. 25 In primary breast cancer, ER positivity is currently defined as ≥1% positive tumour cell nuclei according to the American Society of Clinical Oncology/College of American Pathologists guideline recommendations, 26,27 based on the lack of benefit from hormonal therapy in patients with tumours with <1% positivity.…”

Section: Discussionmentioning

confidence: 99%

“…Among lung cancer specimens, PgR expression has been reported in 0-47%. 19,21,37,38 Again, some of this variability may be attributable to the use of different antibody clones. 30 Unlike in breast cancer, where PgR and ER are often coexpressed, PgR-positive NSCLCs were reported to be rarely ERpositive, suggesting an ER-independent mechanism of PgR expression in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

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Immunohistological expression of oestrogen receptor, progesterone receptor, mammaglobin, human epidermal growth factor receptor 2 and GATA‐binding protein 3 in non‐small‐cell lung cancer

et al. 2020

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Aims: Non-small-cell lung cancer (NSCLC) and breast cancer are common entities. Staining for oestrogen receptor (ER), progesterone receptor (PgR), mammaglobin (MAMG) and GATAbinding protein 3 (GATA3) is frequently performed to confirm a mammary origin in the appropriate diagnostic setting. However, comprehensive data on the immunohistological expression of these markers in NSCLC are limited. Therefore, the aim of this study was to analyse a large cohort of NSCLCs and correlate the staining results with clinicopathological variables. Methods and results: A tissue microarray was stained for ER, PgR, MAMG, human epidermal growth factor receptor 2 (HER2), and GATA3, and included 636 adenocarcinomas (ADCs), 536 squamous cell carcinomas (SqCCs), 65 large-cell-carcinomas, 34 pleomorphic carcinomas, and 20 large-cell neuroendocrine carcinomas. HER2 status was determined for immunohistochemically positive cases with chromogenic in-situ hybridisation. Markers with a proportion of ≥5% positive cases in ADC and SqCC were considered for survival analysis. Among ADCs, 62 (10%), 17 (3%), one (<1%), seven (1%), and 49 (8%) cases were positive for ER, PgR, MAMG, HER2, and GATA3, respectively. Among SqCCs, 10 (2%), 14 (3%), two (<1%) and 109 (20%) cases were positive for ER, PgR, HER2, and GATA3, but none of the

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“…The frequency of ER expression in lung adenocarcinoma has been reported to vary from 7.6% to 27.2%, depending on the antibody used[48]. TTF-1 is positive in 73%–88% of lung adenocarcinoma cases, and there are very few reports of its positivity in breast cancer (less than 3% at least weakly or focally)[49]. Napsin A staining has been reported to be positive in 80%-90% of lung adenocarcinoma cases.…”

Section: Discussionmentioning

confidence: 99%

Breast metastasis from primary lung adenocarcinoma in a young woman: A case report and literature review

Enrico¹,

Saucedo²,

Bravo³

2019

WJCO

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BACKGROUND Breast metastasis from extra mammary malignancies is rare. An incidence of 0.2%-1.3% has been reported in the literature, including that from different types of malignant neoplasms. CASE SUMMARY We present a case of a 29-year-old nonsmoking woman with breast metastasis from lung adenocarcinoma. Computed tomography revealed atelectasis in the right middle lobe of the lung and ipsilateral pleural effusion. Additionally, on physical examination, a small mass was noted in her right breast. The patient underwent bronchoscopy, needle thoracentesis, and breast biopsy. Following cytology, histology and immunohistochemistry, primary lung adenocarcinoma with metastasis to the breast was diagnosed. Only 63 cases, including our patient, have been reported in the literature since 2000, and this is the second in a woman under 30 years of age. CONCLUSION This atypical presentation may cause a significant diagnostic dilemma, but the contribution of immunohistochemistry is crucial to the accuracy of the final diagnosis.

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Differential expression of immunohistochemical markers in primary lung and breast cancers enriched for triple‐negative tumours

Abstract: An immunohistochemical panel incorporating ER, TTF-1, GCDFP-15, p63 and WT1 can help to distinguish lung cancer from metastatic breast cancer, including TNBC.

Cited by 20 publications

References 57 publications

DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer

DNA methylation landscape of triple-negative ductal carcinoma in situ (DCIS) progressing to the invasive stage in canine breast cancer

Immunohistological expression of oestrogen receptor, progesterone receptor, mammaglobin, human epidermal growth factor receptor 2 and GATA‐binding protein 3 in non‐small‐cell lung cancer

Breast metastasis from primary lung adenocarcinoma in a young woman: A case report and literature review

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