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.
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.
Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that is generally indolent, however, could advance to invasive carcinoma in more than one-third of cases if left untreated. ...Thus, there is continuous research to find DCIS characteristics that would enable clinicians to decide if it could be left without intensive treatment. Neoductgenesis (i.e., formation of the new duct of improper morphology) is a promising, but still not sufficiently evaluated indicator of future tumor invasiveness. We gathered data from 96 cases of DCIS (histopathological, clinical, and radiological) to assess the relationship between the neoductgenesis and well-established features of high-risk tumor behavior. Furthermore, our intention was to determine which degree of neoductgenesis should be considered clinically significant. Our major finding was that neoductgenesis is strictly related to other characteristics that indicate the invasive potential of the tumor and, to achieve more accurate prediction, neoductgenesis should be accordingly recognized to less strict criteria. Therefore, we conclude that neoductgenesis is another important revelator of tumor malignancy and that it requires further investigation during prospective controlled trials.
Diffuse pleural mesothelioma (PM) is a highly aggressive tumour typically associated with short survival. Recently, the effectiveness of first‐line immune checkpoint inhibitors in patients with ...unresectable PM was reported. CD70–CD27 signalling plays a co‐stimulatory role in promoting T cell expansion and differentiation through the nuclear factor κB (NF‐κB) pathway. Conversely, the PD‐L1 (CD274)–PD‐1 (PDCD1) pathway is crucial for the modulation of immune responses in normal conditions. Nevertheless, pathological activation of both the CD70–CD27 and PD‐L1–PD‐1 pathways by aberrantly expressed CD70 and PD‐L1 participates in the immune evasion of tumour cells. In this study, 171 well‐characterised PMs including epithelioid (n = 144), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, PD‐L1, and immune cell markers such as CD3, CD4, CD8, CD56, PD‐1, FOXP3, CD68, and CD163. Eight percent (14/171) of mesotheliomas simultaneously expressed CD70 and PD‐L1 on the tumour cell membrane. PMs co‐expressing CD70 and PD‐L1 contained significantly higher numbers of CD8+ (p = 0.0016), FOXP3+ (p = 0.00075), and CD163+ (p = 0.0011) immune cells within their microenvironments. Overall survival was significantly decreased in the cohort of patients with PM co‐expressing CD70 and PD‐L1 (p < 0.0001). In vitro experiments revealed that PD‐L1 and CD70 additively enhanced the motility and invasiveness of PM cells. In contrast, PM cell proliferation was suppressed by PD‐L1. PD‐L1 enhanced mesenchymal phenotypes such as N‐cadherin up‐regulation. Collectively, these findings suggest that CD70 and PD‐L1 both enhance the malignant phenotypes of PM and diminish anti‐tumour immune responses. Based on our observations, combination therapy targeting these signalling pathways might be useful in patients with PM.
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.
Dendritic cells are crucial for cutaneous immune response. Their role in melanoma progression is however a matter of controversy.
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.
Average peritumoral CD207+ cells count was 22.88 for all cases, 17.94 for
lesions and 26.24 for invasive cases. Average epidermal CD207+ cells count was 164.47 for all cases, 183.00 for
lesions and 150.78 - for invasive cases. In case of invasive melanomas, peritumoral CD207+ cells count was positively correlated with Breslow stage (
= 0.59) mitotic activity within the tumor (
= 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).
CD207+ cells play a role in both progression and regression of melanoma but their exact role needs further studies.
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.
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/mm
and chymase-positive cells 9.91/mm
. The average number of CD31+ vascular profiles was 352.66/mm
. The average number of tryptase-positive cells was 26.35/mm
for ERG- cases and 32.12/mm
for ERG+ cases. The average number of chymase-positive cells was 8.14/mm
for ERG- cases and 12.06/mm
for ERG+ cases. The average number of CD31+ vascular profiles was 321.34/mm
for ERG- cases and 390.74/mm
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.
T lymphocytes are the most numerous immune cells in tumor-associated infiltrates and include several subpopulations of either anticancer or pro-tumorigenic functions. However, the associations ...between levels of different T cell subsets and breast cancer molecular subtypes as well as other prognostic factors have not been fully established yet. We performed immunohistochemistry for CD8 (cytotoxic T cells (CTL)), FOXP3 (regulatory T cells (Tregs)), and GATA3 (Th2 cells) in 106 formalin-fixed paraffin-embedded invasive breast cancer tissue samples and analyzed both the numbers and percentages of investigated cells in tumor-associated infiltrates. We observed that triple-negative breast cancer (TNBC) and HER2+ non-luminal breast tumors were associated with more numerous CTLs and Tregs and a higher Treg/Th2 cell ratio as compared with luminal A subtype. A higher Treg percentage was related to a decreased hormone receptor expression, an increase in the Ki67 level, a greater tumor size of luminal tumors, and the presence of lymph node metastases. Moreover, differences in the composition of T cell infiltrates were associated with HER2 status and histologic grade and type, and a distinct immune pattern was observed in tumors of different phenotypes regarding pT stage and nodal status. The results of our work show the diversity of T cell infiltrates in primary invasive breast cancers of different phenotypes and suggest that progression of luminal or non-luminal tumors is related to distinct tumor-associated T cell composition.
The aim of the study was to assess the value of vascular endothelial growth factor (VEGF) measurements in breast cancer patients with respect to recognized clinicopathological prognostic factors. The ...study was conducted in 87 women with histologically confirmed breast cancer who underwent surgical treatment and 37 healthy women. Vascular endothelial growth factor concentration levels in the blood samples of patients were correlated with the size of the primary tumor, lymph nodes in the armpit, cancer stage, histological type, grading, multifocality, status of estrogen and progesterone receptors and HER-2 protein expression. Statistical analysis did not show any correlation between concentrations of VEGF and any of the selected parameters. The comparison of VEGF concentrations showed a slightly raised level of VEGF in women with the disease as opposed to the healthy subjects but the differences were not statistically significant (p = 0.472). Similar results were obtained for marker CEA (p = 0.09), while the level of Ca 15-3 in both groups differed significantly (p < 0.001) reaching higher values in the patients with diagnosed breast cancer. Vascular endothelial growth factor concentrations in breast cancer patients do not correlate with recognized clinicopathological prognostic factors and CEA and Ca 15-3 markers, which does not preclude the potential role of VEGF as an independent prognostic factor.
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