Immunohistochemical demonstration of oestrogen and progesterone receptors in paraffin sections of breast carcinoma

Mesothelin is a cell surface glycoprotein that is overexpressed in various malignancies. Recent studies have revealed that mesothelin plays an oncogenic role in tumor growth and drug resistance through the Wnt/NF-κB/PI3K/Akt signaling pathways. Herein, the expression of mesothelin in HER2-positive and triple-negative breast cancer (TNBC) has been correlated with prognosis.

A total of 430 patients with breast cancer treated between 2006 and 2013 were retrospectively reviewed; of these, 123 cases were considered TNBC (n = 71; 58%) or were positive for HER2 (n = 52; 42%). Mesothelin expression was assessed by immunohistochemistry.

Of the patients with TNBC, 30 (42.3%) were positive for mesothelin expression, compared to only two (3.8%) of the HER2-positive cases. As most HER2-positive tumors were negative for mesothelin staining, statistical analysis was not performed. Median overall survival (OS) was 70.1 months for patients with TNBC, whereas median OS was 70.1 months, in the mesothelin-positive group and 74.5 months in mesothelin-negative group, respectively. Strong correlation was seen between mesothelin expression and tumor grade in patients with TNBC (P < 0.005). In a multivariable Cox proportional hazards model, mesothelin expression was not independently associated with OS in patients with TNBC.

Expression of mesothelin was observed in 42.3% of patients with TNBC and demonstrated a strong association with tumor grade. However, its expression was not correlated with prognosis.

Mesothelin is an ideal tumor-associated marker for the development of targeted therapy due to its limited expression in normal tissues. The aim of this study was to evaluate mesothelin expression in triple-negative breast cancer (TNBC) and its correlation with survival outcomes.

Mesothelin expression was completed by using immunohistochemistry and was quantified by the H score. An H score > 10 was considered positive. Patient characteristics were compared by mesothelin expression. The Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics.

The median age was 52 years. Of the 109 patients with TNBC, 37 (34%) were positive for mesothelin expression. There were no differences on patient and/or tumor characteristics by mesothelin expression with the exception of high frequency of lymphovascular space invasion in mesothelin-negative tumors (2P = .03). At a median follow-up of 75.8 months, 20 (18.3%) patients had experienced a recurrence, and 22 (20.2%) had died. Five-year progression-free survival was 87% and 92% in patients with mesothelin-positive and those with mesothelin-negative tumors (2P = .43). Five-year overall survival was 85% and 91% in patients with mesothelin-positive and those with mesothelin-negative tumors (2P = .57), respectively. Mesothelin expression was not an independent predictor of survival outcomes.

Mesothelin expression was identified in 34% of patients with TNBC. Mesothelin expression did not correlate with survival outcomes in patients with TNBC.

To establish the suitability of multiplex tandem polymerase chain reaction (MT-PCR) for rapid identification of oestrogen receptor (ER) and Her-2 status using a single, formalin-fixed, paraffin-embedded (FFPE) breast tumour section.

Tissue sections from 29 breast tumours were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). RNA extracted from 10 μm FFPE breast tumour sections from 24 of 29 tumours (14 ER positive and 5 Her-2 positive) was analysed by MT-PCR. After establishing a correlation between IHC and/or FISH and MT-PCR results, the ER/Her-2 status of a further 32 randomly selected, archival breast tumour specimens was established by MT-PCR in a blinded fashion, and compared to IHC/FISH results.

MT-PCR levels of ER and Her-2 showed good concordance with IHC and FISH results. Furthermore, among the ER positive tumours, MT-PCR provided a quantitative score with a high dynamic range. Threshold values obtained from this data set applied to 32 archival tumour specimens showed that tumours strongly positive for ER and/or Her-2 expression were easily identified by MT-PCR.

MT-PCR can provide rapid, sensitive and cost-effective analysis of FFPE material and may prove useful as triage to identify patients suited to endocrine or trastuzumab (Herceptin) treatment.

The results of H-scores of oestrogen and progesterone receptor (ER and PR) expression in 150 invasive breast cancers were correlated with conventional pathological prognostic parameters: tumour size, histological grade and subtype, lymph node status, lymphovascular invasion, Nottingham Prognostic Index (NPI) and pathological stage. ER and PR status was determined by immunohistochemical staining of sections cut from archival paraffin-embedded tissue blocks. We defined positive receptor expression as a H-score of 50 and above. Our findings revealed ER and PR positivity in 98 (65%) and 52 (35%) cases, respectively. Fifty-one (34%) ER-positive cases also showed PR expression, while 51 (34%) tumours were negative for both ER and PR. Positive expression for ER and PR was significantly correlated with histological grade (P < 0.0005), mitotic score (P < 0.05) and nuclear pleomorphism (P < 0.05). When we used the relatively simpler method of a cut off of at least 10% tumour cell nuclear staining of moderate or greater intensity as positive receptor status, we found that it agreed well with results of the H-score, a more quantitative method of assessment.

The role of the surgical pathologist in dealing with breast biopsies has changed enormously during the last few years. The introduction of mammographic screening, conservative breast surgery, core biopsies and, more recently, sentinel lymph node techniques, have changed the type of material received by the pathologist for diagnosis, and the type of information required from him/her. Requests for frozen sections have markedly diminished, but new challenges have arisen, particularly in respect of diagnosing borderline lesions which are being increasingly detected by mammography. This article presents a detailed account of the handling and reporting of breast biopsies, based partly on National Guidelines and the practice at Charing Cross Hospital, London.