Comparison of immunoreactive score, HER2/<i>neu</i> score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms

Specht, Elisa; Kaemmerer, Daniel; Sänger, Jörg; Wirtz, Ralph M.; Schulz, Stefan; Lupp, Amelie

doi:10.1111/his.12662

Cited by 135 publications

(93 citation statements)

References 34 publications

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“…3,36,37 We further evaluated expression of SSTRs using an IHCS system that differentiates between high and low expression. 26,31–33 SSTR2 was highly expressed in 51% of cases, followed by SSTR1 (47%) and SSTR5 (43%); while the remaining SSTR4 (36%) and SSTR3 (23%) generally had low expression levels. High expression of SSTR1 and SSTR2 was more frequently observed in pancreatic NETs and small intestinal NETs than in other NETs.…”

Section: Discussionmentioning

confidence: 98%

“…The antibodies used for SSTRs 1, 2, 3, and 5 in this study have been previously used and validated. 25,26 In our studies, normal pancreatic islet cells, which are known to be positive for SSTRs 1-5, were used as positive controls. 27,28 We used omission of the primary antibody as one method of negative control for SSTRs 1-5.…”

Section: Methodsmentioning

confidence: 99%

“…Membranous expression of SSTR2, and the assessed-combined expression of cytoplasmic and membrane staining of the receptor proteins SSTR1, SSTR3, SSTR4, and SSTR5 were scored by applying a semi-quantitative immunohistochemistry scoring (IHCS) system, as previously described. 26,31–33 In brief, staining intensity was scored as 0 (no immunostaining), 1 (weak), 2 (moderate) or 3 (strong). The percentage of immunoreactive cells was scored as 0 (none), 1 (< 10%), 2 (10–50%), 3 (51–80%) or 4 (> 80%).…”

Section: Methodsmentioning

confidence: 99%

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Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Qian

Ter‐Minassian

et al. 2016

Pancreas

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Objective Somatostatin receptors (SSTRs), products of gene superfamily SSTR1-5, are commonly expressed in neuroendocrine tumors (NETs). Somatostatin analogs (SSAs) bind to SSTRs and are used as therapeutic agents in patients with advanced NETs. We hypothesized that tumor SSTR expression status would be associated with clinical outcomes in NET. Methods Expression of the five SSTRs was evaluated by immunohistochemistry, using tissue microarrays comprising 173 primary NETs, 24 matched metastases, and 22 metastatic NETs from 195 patients. Cox proportional hazards regression analysis was used to assess the association of SSTR expression status (high vs. low) with clinical outcomes, adjusting for potential confounders. Results High expression of SSTR2 was associated with longer overall survival in the cohort overall (multivariate hazard ratio 0.42, 95% confidence interval 0.21–0.84; P = 0.013). In a subgroup of patients with metastatic small intestine NET treated with SSAs and evaluable for progression, SSTR2 expression was associated with both longer progression-free and overall survival. No associations with progression-free or overall survival were observed with expression of other SSTRs. Conclusions Our study demonstrated that expression of SSTR2, but not other SSTRs, is associated with longer overall survival. In patients treated with SSAs, expression of SSTR2 is associated with longer progression-free survival.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Qian

Ter‐Minassian

et al. 2016

Pancreas

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“…The number of stained cells was reported as a percentage of all malignant cells. A histological sum score, the H score, was computed by multiplying the intensity and staining percentage scores, resulting in a scale 0-300 [22]. Separate H scores were created for nuclear, cytoplasmic, and membranous immunostaining.…”

Section: Staining Proceduresmentioning

confidence: 99%

Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A

et al. 2018

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Objectives: Due to the rarity of breast carcinomas with neuroendocrine features (NEBC), the knowledge on their biology is very limited but the identification of their biology and prognostic factors is essential to evaluate both pathogenesis and possible targeted treatment options. We assessed the expression of the well-characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in NEBC. Methods: We assessed the immunohistochemical expression of neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive ductal carcinomas (IDC). Results: Nuclear and cytoplasmic TS, nuclear and cytoplasmic NSE, and nuclear p27 had significant overexpression in NEBC compared with IDC (for all, p < 0.01). In NEBC, cytoplasmic SSTR-2A expression was associated with excellent distant disease-free survival (p = 0.013), cytoplasmic menin expression with poorer relapse-free survival (p = 0.022), and nuclear p27 with longer breast cancer-specific survival (p = 0.022). Conclusions: There is a striking similarity in GEP-NET and NEBC regarding prognostic factors. GEP-NET and NEBC also appear to show similar expression patterns of the studied markers, while there are notable differences compared to IDC. Due to the wide expression of SSTR-2A, the treatment option with somatostatin analogs in NEBC should be evaluated.

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“…Galectin-1 and galectin-3 expression by tumor cells were analyzed using an immunoreactive score (IRS; ref. 21), taking into account the percentage of positive cells and the intensity of the staining (Supplementary Table S1A). …”

Section: Immunofluorescence and Ihcmentioning

confidence: 99%

Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature

Melief

Visconti

Visser

et al. 2017

Cancer Immunology Research

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The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9. Single factors associated with better survival were identified using Kaplan-Meier curves and multivariate Cox regression analyses, and those factors were used for interaction analyses. The results were validated using The Cancer Genome Atlas database. We identified four parameters that were associated with a better survival: CD8þ T cells, galectin-macrophage ratio, and the expression of galectin-3 by tumor cells. The presence of at least three of these parameters formed an independent positive prognostic factor for long-term survival. Patients displaying this four-parameter signature were found exclusively among patients responding to ACT and were the ones with sustained clinical benefit.

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Comparison of immunoreactive score, HER2/neu score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms

Abstract: Because a unified IHC scoring system for SSTR analysis is needed urgently to optimize the theranostics of NEN, among the scores tested, the IRS seems to be the most suitable according to our results. It provides sufficient accuracy combined with high practicability.

Cited by 135 publications

References 34 publications

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A

Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature

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