Characterization of Pleural Mesothelioma by Hierarchical Clustering Analyses Using Immune Cells within Tumor Microenvironment.

INTRODUCTION: Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated. METHODS: In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers: CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1, and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed. RESULTS: Among the immune cell markers, CD3 (p < 0.0001), CD4 (p = 0.0016), CD8 (p = 0.00094), CD163+ (p = 0.042), and FOXP3+ (p = 0.025) were significantly associated with an unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (p = 0.050), CD27 (p = 0.014), and TIM-3 (p = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (p = 0.016): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (p = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04), and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients. CONCLUSION: Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.

Treatment outcomes and prognostic factors in nonmetastatic metaplastic breast cancer patients: a multicenter retrospective cohort study.

BACKGROUND AND PURPOSE: Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. MATERIALS AND METHODS: In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. RESULTS: Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. INTERPRETATION: Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.

Enhancing diagnostic precision: comparative analysis of MR-guided breast biopsies performed in two centres.

Purpose: Breast lesions that remain elusive in traditional imaging techniques such as ultrasound and mammography pose a diagnostic challenge. In such cases, magnetic resonance (MR)-guided breast biopsy emerges as a crucial tool for accurate histopathological verification. This article presents a comparative study conducted at 2 centres, exploring the results of MR-guided breast biopsies performed by experienced radiologists, based on inside and external referrals. Material and methods: The study involved 228 patients, 120 of whom underwent biopsies at Centre 1, where the same radiologist performed both the qualification and biopsy. The remaining 108 patients were biopsied at Centre 2, based on referrals from different institutions. Uniform examination protocols were adopted at both centres, and all biopsies underwent histopathological verification. Results: The distribution of lesion types was found to be independent of the apparatus used for biopsies (p = 0.759). Interestingly, Centre 1 exhibited a higher prevalence of infiltrating carcinomas compared to Centre 2 (p = 0.12). Furthermore, the analysis demonstrated a significant variance in the nature of the lesions in relation to breast structure and biopsy centre (p < 0.001). Conclusions: MR-guided breast biopsy serves as a remarkable tool for verifying lesions that evade detection through conventional imaging methods and physical examinations. The study findings underscore the crucial role of radiologist experience in determining the efficacy of MR-guided breast biopsies.

Variabilities in global DNA methylation and ß-sheet richness establish spectroscopic landscapes among subtypes of pancreatic cancer.

PURPOSE: Knowledge about pancreatic cancer (PC) biology has been growing rapidly in recent decades. Nevertheless, the survival of PC patients has not greatly improved. The development of a novel methodology suitable for deep investigation of the nature of PC tumors is of great importance. Molecular imaging techniques, such as Fourier transform infrared (FTIR) spectroscopy and Raman hyperspectral mapping (RHM) combined with advanced multivariate data analysis, were useful in studying the biochemical composition of PC tissue. METHODS: Here, we evaluated the potential of molecular imaging in differentiating three groups of PC tumors, which originate from different precursor lesions. Specifically, we comprehensively investigated adenocarcinomas (ACs): conventional ductal AC, intraductal papillary mucinous carcinoma, and ampulla of Vater AC. FTIR microspectroscopy and RHM maps of 24 PC tissue slides were obtained, and comprehensive advanced statistical analyses, such as hierarchical clustering and nonnegative matrix factorization, were performed on a total of 211,355 Raman spectra. Additionally, we employed deep learning technology for the same task of PC subtyping to enable automation. The so-called convolutional neural network (CNN) was trained to recognize spectra specific to each PC group and then employed to generate CNN-prediction-based tissue maps. To identify the DNA methylation spectral markers, we used differently methylated, isolated DNA and compared the observed spectral differences with the results obtained from cellular nuclei regions of PC tissues. RESULTS: The results showed significant differences among cancer tissues of the studied PC groups. The main findings are the varying content of ß-sheet-rich proteins within the PC cells and alterations in the relative DNA methylation level. Our CNN model efficiently differentiated PC groups with 94% accuracy. The usage of CNN in the classification task did not require Raman spectral data preprocessing and eliminated the need for extensive knowledge of statistical methodologies. CONCLUSIONS: Molecular spectroscopy combined with CNN technology is a powerful tool for PC detection and subtyping. The molecular fingerprint of DNA methylation and ß-sheet cytoplasmic proteins established by our results is different for the main PC groups and allowed the subtyping of pancreatic tumors, which can improve patient management and increase their survival. Our observations are of key importance in understanding the variability of PC and allow translation of the methodology into clinical practice by utilizing liquid biopsy testing.

Enhanced Detection of Suspicious Breast Lesions: A Comparative Study of Full-Field Digital Mammography and Automated Breast Ultrasound in 117 Patients with Core Needle Biopsy.

BACKGROUND This retrospective study from a single center aimed to compare the performance of full-field digital mammography (FFDM) vs automated breast ultrasound (ABUS) in the identification and characterization of suspicious breast lesions in 117 patients who underwent core-needle biopsy (CNB) of the breast. MATERIAL AND METHODS The study involved a group of 301 women. Every patient underwent FFDM followed by ABUS, which were assessed in concordance with BI-RADS (Breast Imaging Reporting and Data System) classification. RESULTS No focal lesions were found in 168 patients. In 133 patients, 117 histopathologically verified focal lesions were found. Among them, 78% appeared to be malignant and 22% benign. ABUS detected 246 focal lesions, including 115 classified as BI-RADS 4 or 5 and submitted to verification, while FFDM revealed 122 lesions, including 75 submitted to verification. The analysis revealed that combined application of both methods caused sensitivity to increase to 100, and improved accuracy improvement. Margin assessments in these examinations are consistent (P<0.00), the lesion's margin type with both methods depends on its malignant or benign character (P<0.03), lesion margins distribution on ABUS depends on estrogen receptor presence (P=0.033), and there was significant correlation between malignant character of the lesion and retraction phenomenon sign (P=0.033). ABUS obtained higher compliance between the size of the lesion in histopathology compared to FFDM (P>0.05). CONCLUSIONS The results shows that ABUS is comparable to FFDM, and even outperforms it in a few of the analyzed categories, suggesting that the combination of these 2 methods may have an important role in breast cancer detection.

Breast carcinoma grading on core needle biopsy - to grade or not to grade?

Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease and the basis for the treatment planning. The concordance rate between CNB and surgical excision specimen in determination of histological grade (HG) varies widely across literature, ranging from 59-91%. The aim of our study was to investigate the level of concordance between CNB and surgical excision specimen for the determination of HG for breast cancer patients. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. The concordance level between core needle biopsy and surgical resection specimen for overall histologic grading was 73%: for tubule formation - 71%, for nuclear pleomorphism - 91%, for the mitotic index - 59%. Our study shows that our institution's histologic grading of CNBs and surgical excisions shows a fairly good correlation and is useful for the planning of treatment.

No differences in miRNA expression in the stroma of ERG+ and ERG- prostate cancers.

Prostate cancer (PC) is one of the most common cancers in males. A significant proportion of PCs bear TMPRSS2-ETS translocation and overexpress ERG transcription factor, allowing classification into ERG+ and ERG- groups, which differ in several features including the tumor microenvironment. The aim of the study was to verify whether they differ in expression of the miRNA in the microenvironment. The material consisted of 150 radical prostatectomies. Immunohistochemistry (IHC) for ERG was done using a routine method. FISH for TMPRSS2-ETS translocation was done with a ZytoLight SPEC ERG/TMPRSS2 TriCheck Probe. From each case, a representative section was selected, and tumor and non-tumor were microdissected with the LMD7000 device. RNA was isolated using the RNeasy Mini Kit system (Qiagen) and miRNA libraries were prepared with the NEBNext Multiplex Small RNA Library Prep Set for Illumina and their sequencing was performed on the NexSeq 500. Statistical analysis was done with Statistica and R software. When analyzing the expression of miRNAs some differences could be seen, but after correction for multiple comparisons was applied, these were found to be non- significant.

Distribution of DC Subtypes: CD83+, DC-LAMP+, CD1a+, CD1c+, CD123+, and DC-SIGN+ in the Tumor Microenvironment of Endometrial Cancers-Correlation with Clinicopathologic Features.

Treatment options for endometrial cancer (EC) do not provide satisfactory survival improvement for advanced cases, hence the interest in novel therapies utilizing immunological regulatory mechanisms. Measures to modify the functionality of dendritic cells (DCs) found in TME are intensively investigated, given that DCs play a crucial role in inducing antitumor immunity. Samples of malignant endometrial neoplasms obtained from 94 patients were immunohistochemically stained with selected antibodies. Counts of positively identified DCs were correlated with clinical advancement and histological malignancy of cancers. The most prominent DC subtypes were immature DC-SIGN+ or CD123+. Mature CD83+ DCs were the fewest. We found a significant divergence of grade value distribution between cancers of different DCs' CD1a+ counts. The DC-LAMP+ count was positively associated with grade. Cancers with the least DC CD1c+ or DC CD123+ had higher pT scores than ones that were more heavily infiltrated. ECs can suppress immune cells, hence the predominance of immature DCs in our samples. Associations between DC counts and clinicopathological features of EC were observed only for a few subsets, which was plausibly due to the low diversity of the obtained samples or the small group size. Predictive abilities of particular DC immune subsets within EC's TME remain ambiguous, which calls for further research.

Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy-An Observational Study.

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.

Dendritic Cell Subpopulations Are Associated with Morphological Features of Breast Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area.

Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden.

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.

CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness.

Diffuse malignant mesothelioma of the pleura (MPM) is a highly aggressive tumour that typically is associated with short survival. CD70 and CD27 belong to the tumour necrosis factor (TNF) and the TNF receptor (TNFR) superfamily, respectively. Under physiological conditions, the tightly regulated interaction between CD70 and CD27 plays a co-stimulatory role in promoting T-cell expansion and differentiation through the NFκB pathway. Aberrantly high CD70 expression has been documented in haematological and solid malignancies in association with immune evasion in malignant cells. In this study, 172 well-characterised primary diffuse MPM tumours including epithelioid (n = 145), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, CD27, CD3, CD4, CD8, CD56, PDCD1 (PD-1), and FOXP3 expression. Twenty per cent (34/172) of the mesothelioma cells expressed CD70 on the cell membrane. Overall survival was significantly decreased in the cohort of patients with CD70-expressing tumour cells (p < 0.01). Patients with MPM containing a higher number of CD3+ (p < 0.01), CD4+ (p < 0.01), CD8+ (p < 0.01), or FOXP3+ (p < 0.01) tumour-infiltrating lymphoid cells (TILs) showed significantly worse clinical outcomes. As potential independent risk factors for MPM patients, multivariate Cox proportional hazards regression analysis revealed CD70 expression on mesothelioma cells [hazard ratio (HR) 2.25; p = 0.010], higher FOXP3+ TILs (HR 2.81; p = 0.004), and higher CD3+ TIL accumulation (HR 6.12; p < 0.001). In contrast, as a potential independent favourable factor, higher CD27+ TIL accumulation (HR 0.48; p = 0.037) was identified. In vitro experiments and an immunodeficient mouse model revealed that CD70 enhances the invasiveness of MPM cells through MET-ERK axis activation. Further analyses in syngeneic mouse models demonstrated possible roles for CD70 in immune evasion. Collectively, these findings suggest that the CD70-CD27 pathway enhances the malignant phenotypes of MPM and diminishes anti-tumor immune response in patients with these neoplasms. These markers might be useful in MPM for prognostic evaluations as well as targeted therapeutics. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Primary bilateral angiosarcoma of the breast treated with neoadjuvant chemotherapy combined with propranolol.

A case report of bilateral primary angiosarcoma treated with neoadjuvant chemotherapy was presented. A routine diagnostic mammography and ultrasound examinations indicated abnormalities in both breasts of the patient, confirmed on MRI as large bilateral masses. Core needle biopsy revealed angiosarcoma G1. The treatment agreed during the interdisciplinary meeting involved chemotherapy combined with simultaneous blockade of beta-adrenergic receptors, followed by bilateral simple mastectomy. This case highlights the importance of a patient-focused care.

Image analysis discloses differences in nuclear parameters between ERG+ and ERG- prostatic carcinomas.

Prostatic carcinoma (PC) is the most frequent urologic cancer and one of the most frequent cancers in males; it is a heterogeneous disease, in terms of molecular features, morphology and prognosis. About half of cases depends on TMPRSS2-ETS translocation which leads to a production of ERG transcription factor. ERG+ and ERG- cancers seem to differ in a number of features, which could lead to an altered nuclear structure; the aim of the study was to test this hypothesis. The material consisted of total 39 PC cases, representing ERG+ and ERG-, as well as Gleason pattern 3 and 4. Filtering by color deconvolution and automatic segmentation were used, and the properly detected nuclei were manually selected. From each case fifty nuclei were obtained; then geometric features and texture parameters were assessed. The analysis of the collected data showed differences both between ERG+/ERG- and Gleason pattern 3 and 4 cases in most of the features analyzed. Our results suggest that indeed the ERG status, thus likely TMPRSS2-ETS translocation, has an impact on morphology of nuclei in PC, and their differences are evident enough to be detectable by image analysis.

Lymphoid environment in molecular subtypes of breast cancer.

Recently, a large body of evidence has shown that the microenvironment of invasive breast carcinoma affects its development and the patient's outcome, and vice versa - cancer cells express factors that modulate tumour milieu in terms of its composition and function. We performed an immunohistochemical (IHC) staining of 108 formalin-fixed, paraffin-embedded (FFPE) tissue samples to investigate the relationships between T-cell, B-cell, and NK-cell infiltrate, invasive breast carcinomas molecular subtypes, and other prognostic indicators. The main findings of our study were as follows: the significantly higher infiltrate of the analysed immune cell subsets in triple-negative (TNBC), HER2-positive, non-luminal and luminal B/HER2+ breast carcinomas than in luminal A cancers; their higher densities in poorly differentiated lesions; correlations between lymphoid cells and the expression of hormonal receptors, HER2 receptor status, and marker of cancer proliferation. Furthermore, we observed T-cell numbers to be associated with greater tumour diameter. In summary, the results of our study indicate associations between tumoural lymphoid infiltration and the unfavourable intrinsic subtypes as well as other detrimental prognostic factors in invasive breast carcinomas.

The relationship between breast cancer treatment, tumour type and vitamin D level in pre- and postmenopausal women.

OBJECTIVE: Vitamin D deficiency has been linked to a higher risk of cancer. There is insufficient data regarding the influence of treatment on vitamin D status. The aim of this study was to compare pre- and post-treatment levels of 25(OH)D in premenopausal and postmenopausal women with breast cancer with a different receptor status (ER-estrogen receptors, PR-progesterone receptors) and in healthy controls. METHODS: 49 patients with breast cancer (23 premenopausal), and 28 healthy controls matched for age, menopausal status and BMI. RESULTS: The pre-treatment levels of 25(OH)D in patients with breast cancer were significantly lower in comparison to the control group (19 ng/mL vs. 30 ng/mL, p<0.001), the lowest in premenopausal women (18.4 ng/mL). After the treatment period, a significant decrease in 25(OH)D level (mean 15.8 ng/mL) was observed. The pre-treatment level of 25(OH)D was significantly lower in patients with ER (16.1 vs. 23.9 ng/mL, p=0.02) and with PR (15 vs. 24.4 ng/mL, p=0.003). The mean pre- and post-treatment levels of 25(OH)D were lower in patients with Ki67 <21% (16.7 vs. 20.1 ng/mL, p=0.15; 12.5 vs. 18.1 ng/mL, p=0.02 respectively). CONCLUSIONS: 25(OH)D level is lower in patients with breast cancer in comparison to healthy women, regardless of their menopausal status. The lowest levels are found in patients with ER and PR positive tumours. While a significant decrease in 25(OH)D level during the course of therapy is observed, the supplementation of vitamin D should be considered.

CD207+/langerin positive dendritic cells in invasive and in situ cutaneous malignant melanoma.

INTRODUCTION: Dendritic cells are crucial for cutaneous immune response. Their role in melanoma progression is however a matter of controversy. MATERIAL AND METHODS: The number of dendritic cells within epidermis and in peri- and intratumoral location was analyzed using CD207 immunostain in 17 cases of in situ and 25 case of invasive melanoma. RESULTS: Average peritumoral CD207+ cells count was 22.88 for all cases, 17.94 for in situ lesions and 26.24 for invasive cases. Average epidermal CD207+ cells count was 164.47 for all cases, 183.00 for in situ lesions and 150.78 - for invasive cases. In case of invasive melanomas, peritumoral CD207+ cells count was positively correlated with Breslow stage (R = 0.59) mitotic activity within the tumor (R = 0.62). Invasive cases with regression showed higher intratumoral and epidermal CD207+ cells count than the ones without (275.00 vs. 95.32 and 173.20 vs. 148.35) but lower peritumoral CD207+ cells count (17.60 vs. 27.26). Invasive cases with ulceration showed higher intratumoral and peritumoral CD207+ cells count than the ones without ulceration (220.08 vs. 55.67 and 44.17 vs. 9.69). CONCLUSIONS: CD207+ cells play a role in both progression and regression of melanoma but their exact role needs further studies.

Prostate cancer with different ERG status may show different FOXP3-positive cell numbers.

Prostatic carcinoma is the most frequent cancer in males in the Western world. A significant proportion of these cancers have a recurrent translocation involving ETS family genes, which leads to the overexpression of ERG transcription factor. Prostate cancers, which bear this mutation, differ in a number of features, including tumor microenvironment. One of the components of the tumor microenvironment is FOXP3 positive lymphocytes, which may participate in breaking immunosurveillance and promoting tumor growth. The aim of the study was to analyze the relationships between ERG expression, number of FOXP3 positive cells and other features of the tumor. The study group consisted of 65 cases. Tissue microarrays composed of 2 mm tissue cores were used for immunohistological evaluation. Immunohistochemistry for ERG and FOXP3 was performed according to the routinely applied protocol. The FOXP3 positive cells were counted and the results were expressed as the number of cells per mm2. The average number of FOXP3 positive cells was 33.30/mm2 for all cases, 21.43/mm2 for the ERG negative and 42.28/mm2 for the ERG positive group (p < 0.02). There were no significant relationships between FOXP3 positive cell count and any other parameters studied. Our results suggest that the immune response may differ between ERG negative and ERG positive prostatic carcinomas.

Mast cells influence neoangiogenesis in prostatic cancer independently of ERG status.

A significant proportion of prostatic adenocarcinomas show recurrent translocation leading to ERG expression. Previously we found that ERG+ cases have higher microvessel density than negative ones. One factor influencing angiogenesis in cancer is mast cells. The aim of the present study was to evaluate the relationship between microvessels, mast cells and ERG status. Tissue microarrays prepared from 113 radical prostatectomy specimens were analyzed with immunohistochemistry for CD31, tryptase and chymase. Vascular profiles and tryptase-positive and chymase-positive cells were counted. The average number of tryptase-positive cells was 28.93/mm2 and chymase-positive cells 9.91/mm2. The average number of CD31+ vascular profiles was 352.66/mm2. The average number of tryptase-positive cells was 26.35/mm2 for ERG- cases and 32.12/mm2 for ERG+ cases. The average number of chymase-positive cells was 8.14/mm2 for ERG- cases and 12.06/mm2 for ERG+ cases. The average number of CD31+ vascular profiles was 321.34/mm2 for ERG- cases and 390.74/mm2 for ERG+ cases. The number of CD31+ vascular profiles was positively correlated with the number of tryptase-positive and chymase-positive cells (R = 0.26 and R = 0.20). In summary, we demonstrated an interrelationship between mast cells, microvascular density and ERG status in prostatic carcinoma.