The Immune Response in Nonmetastatic Axillary Lymph Nodes Is Associated with the Presence of Axillary Metastasis and Breast Cancer Patient Outcome.

Tumor cells can modify the immune response in primary tumors and in the axillary lymph nodes with metastasis (ALN) in breast cancer (BC), influencing patient outcome. We investigated whether patterns of immune cells in the primary tumor and in the axillary lymph nodes without metastasis (ALN) differed between patients diagnosed without ALN (diagnosed-ALN) and with ALN (diagnosed-ALN) and the implications for clinical outcome. Eleven immune markers were studied using immunohistochemistry, tissue microarray, and digital image analysis in 141 BC patient samples (75 diagnosed-ALN and 66 diagnosed-ALN).

Evaluation of cytokeratin-19 in breast cancer tissue samples: a comparison of automatic and manual evaluations of scanned tissue microarray cylinders.

Background: Digital image (DI) analysis avoids visual subjectivity in interpreting immunohistochemical stains and provides more reproducible results. An automated procedure consisting of two variant methods for quantifying the cytokeratin-19 (CK19) marker in breast cancer tissues is presented.

Methods: The first method (A) excludes the holes inside selected CK19 stained areas, and the second (B) includes them.

Development of automated quantification methodologies of immunohistochemical markers to determine patterns of immune response in breast cancer: a retrospective cohort study.

Introduction: Lymph nodes are one of the main sites where an effective immune response develops. Normally, axillary nodes are the first place where breast cancer produces metastases. Several studies have demonstrated the importance of immune cells, especially dendritic cells, in the evolution of breast cancer.

Is it necessary to evaluate nuclei in HER2 FISH evaluation?

A new method that simplifies the evaluation of the traditional HER2 fluorescence in situ hybridization (FISH) evaluation in breast cancer was proposed. HER2 status was evaluated in digital images (DIs) captured from 423 invasive breast cancer stained sections. All centromeric/CEP17 and HER2 gene signals obtained from separated stacked DIs were manually counted on the screen.

Digital image analysis in breast cancer: an example of an automated methodology and the effects of image compression.

In the current practice of pathology, the evaluation of immunohistochemical (IHC) markers represents an essential tool. The manual quantification of these markers is still laborious and subjective, and the use of computerized systems for digital image (DI) analysis has not yet resolved the problems of nuclear aggregates (clusters). Furthermore, the volume of DI storage continues to be an important problem in computer-assisted pathology.

JPEG2000 for automated quantification of immunohistochemically stained cell nuclei: a comparative study with standard JPEG format.

The Joint Photographic Experts Group (JPEG) standard format is one of the most widely used in image compression technologies. More recently, JPEG2000 format has emerged as a state-of-the-art technology that provides substantial improvements in picture quality at higher compression ratios. However, there has been no attempt to date to determine which of the two compression formats produces less variability in the automated evaluation of immunohistochemically stained digital images in agreement with their compression rates and complexity degrees.

Appraisal of immune response in lymphoproliferative syndromes: a systematic review.

In lymphoproliferative syndromes, tumoural-immune cell interactions depend on a number of factors related to tumoural and immune cells. Recent gene expression data tend to confirm the decisive role of the reactive microenvironment in the development and clinical behaviour of lymphoproliferative syndromes, and encourage particular interest in the role of T cells and accessory cells. This systematic review brings together the accumulated knowledge about "immune signatures" in Hodgkin and non-Hodgkin lymphomas.

Effects of image compression on automatic count of immunohistochemically stained nuclei in digital images.

This study investigates the effects of digital image compression on automatic quantification of immunohistochemical nuclear markers. We examined 188 images with a previously validated computer-assisted analysis system. A first group was composed of 47 images captured in TIFF format, and other three contained the same images converted from TIFF to JPEG format with 3x, 23x and 46x compression.

Quantification of diverse subcellular immunohistochemical markers with clinicobiological relevancies: validation of a new computer-assisted image analysis procedure.

Tissue microarray technology and immunohistochemical techniques have become a routine and indispensable tool for current anatomical pathology diagnosis. However, manual quantification by eye is relatively slow and subjective, and the use of digital image analysis software to extract information of immunostained specimens is an area of ongoing research, especially when the immunohistochemical signals have different localization in the cells (nuclear, membrane, cytoplasm). To minimize critical aspects of manual quantitative data acquisition, we generated semi-automated image-processing steps for the quantification of individual stained cells with immunohistochemical staining of different subcellular location.

Tumor-infiltrated immune response correlates with alterations in the apoptotic and cell cycle pathways in Hodgkin and Reed-Sternberg cells.

Purpose: To analyze tumor-microenvironment relationships in Hodgkin lymphoma (HL) as potential determinants in the decision-making process related to the alterations in cell cycle and apoptotic pathways of Hodgkin/Reed-Sternberg (H/RS) cells.

Experimental Design: Based on a cohort of 257 classic HL patients, we carried out a global descriptive correlational analysis and logistic regression study to identify tumor-infiltrated immune cell rate in HL that could be interconnected with genes involved in the regulation of apoptotic/proliferative pathways in H/RS cells.

Results: Our results reveal the existence of a connection between the reactive microenvironment and molecular changes in apoptotic/proliferative pathways in H/RS cells.

Automated quantification of nuclear immunohistochemical markers with different complexity.

Manual quantification of immunohistochemically stained nuclear markers is still laborious and subjective and the use of computerized systems for digital image analysis have not yet resolved the problems of nuclear clustering. In this study, we designed a new automatic procedure for quantifying various immunohistochemical nuclear markers with variable clustering complexity. This procedure consisted of two combined macros.

The presence of STAT1-positive tumor-associated macrophages and their relation to outcome in patients with follicular lymphoma.

Background And Objectives: The presence of tumor-associated macrophages (TAM) is a prognostic factor for survival in follicular lymphoma (FL). Overexpression and/or activation of the signal transducer and activator of transcription 1 (STAT1) in these TAM have also been observed. The aim of this study was to determine the extent to which macrophages are present in FL and to investigate the expression of STAT1 in these cells.

Immunohistochemical patterns of reactive microenvironment are associated with clinicobiologic behavior in follicular lymphoma patients.

Purpose: Recent molecular data have suggested that non-neoplastic cells are powerful modulators that may confer a selective advantage or disadvantage on the outcome of follicular lymphoma (FL) patients.

Patients And Methods: The prevalence of the principal inflammatory and immune-infiltrated cells was measured immunohistochemically in the tissue of 211 FL patients, and associations were sought with their traditional clinicobiologic characteristics.

Results: Our results confirmed the presence of a large number of T lymphocytes (CD4+ and CD8+) and CD57+ cells and, at a moderate level, the presence of TIA-1+ cytotoxic cells, CD68+ macrophages, CD123+ plasmacytoid cells, and FOXP3+ regulatory T cells among the pool of non-neoplastic cells.

Outcome in Hodgkin's lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells.

Purpose: Recent studies of Hodgkin's lymphoma (HL) have suggested that the presence of regulatory T cells in the reactive background may explain the inhibition of the antitumoral host immune response observed in these patients. This study aimed to assess the relevance of regulatory T cells and CTLs present in the background of HL samples in the prognosis of a series of classic HL (cHL) patients.

Experimental Design: Expression of granzyme B and TIA-1 (markers for CTL) and FOXP3 (a marker for regulatory T cells) were evaluated independently by immunohistochemistry in tissue microarrays of 257 cHL patients and correlated with patient outcome.