We aimed to evaluate macrophage infiltration and to identify the status of crown-like structures (CLSs) in mammary adipose tissue of human breast tissue in cases with and without breast cancer.
Methods
Breast adipose tissue was obtained from reduction mammoplasty (N = 56, Group 1), non-neoplastic breast tissue of breast cancer patients (N = 84, Group 2), and breast cancer with adipose stroma (N = 140, Group 3). Immunohistochemical staining of CD68 and CD163 was performed, and the infiltrating macrophages and CLSs within breast adipose tissue were evaluated.
Results
Group 3 had the largest number of CD68-positive (CD68+) and CD163-positive (CD163+) macrophages and CLSs within adipose tissue (P < 0.001). Among Group 3, cases with high levels of CD68+ and CD163+ macrophages commonly had a higher histologic grade (P = 0.016 and P = 0.045), and cases with CD163+ CLSs were correlated with old age (P = 0.042), estrogen receptor negativity (P = 0.013), human epidermal growth factor receptor-2 positivity (P = 0.043), and non-luminal A type (P = 0.039). Upon univariate analysis, high levels of CD163+ macrophages were associated with shorter disease-free survival in node-negative breast cancer patients (P = 0.033), and CD68+ CLSs were associated with shorter overall survival in node-positive breast cancer patients (P = 0.015).
Conclusions
CD68+ and/or CD163+ tumor-associated macrophage infiltration as well as CLSs are present in adipose tissue nearby the breast cancer lesion, and are associated with various clinicopathologic parameters of breast cancer.
Programmed death ligand 1 (PD-L1) is a key protein upregulated by tumor cells to suppress immune responses. Tumor-associated macrophages (TAMs) play a major role in this immunosuppression, but the relationship between PD-L1 expression and TAMs remains unclear in gastric adenocarcinoma (GAC). We simultaneously examined expression of PD-L1 and TAMs in GAC.
Methods
We performed immunohistochemical staining for PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) in 217 GAC samples using a tissue microarray. Expression of PD-L1 and CD68- and CD163-positive cells was evaluated using the Cytoplasmic V2.0 algorithm in Aperio ImageScope software, and logistic regression analysis was used to compare expression patterns between groups.
Results
Thirty-one samples (14%) were positive for PD-L1 expression. The mean (± standard error) rates of infiltration were 6.83 ± 0.38% for CD68-positive cells and 6.16 ± 0.29% for CD163-positive cells. The mean rate of CD163-positive cell infiltration was significantly higher in diffuse GAC than in intestinal GAC (diffuse n = 111, 6.91%; intestinal n = 91, 5.26%; p = 0.006), but the mean rate of CD68-positive cell infiltration was similar between these types (p = 0.38). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive GAC were significantly higher than in PD-L1-negative GAC (CD68 p = 0.0002; CD163 p < 0.0001). In multivariate logistic regression analyses, CD163-positive cell infiltration was associated with PD-L1 expression (odds ratio 1.13; 95% confidence interval 1.02–1.25; p = 0.021).
Conclusion
M2-like macrophage infiltration is highly associated with PD-L1 expression in GAC cells, suggesting that macrophage infiltration can serve as a potential therapeutic target.
We investigated the prognostic role of tumour-associated macrophages (TAMs) in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT).
Methods:
The expression of CD68+, CD163+ and CD11b+ cells was assessed using immunohistochemistry in n=106 pre-treatment tumour biopsy samples and was correlated with clinicopathological characteristics, including T-stage, N-stage, grading, tumour localisation, age and sex as well as local failure-free survival (LFFS), distant metastases-free survival (DMFS), progression-free (PFS), and overall survival (OS). Finally, TAMs expression and vessel density (CD31) were examined in n=12 available early local recurrence samples and compared with their matched primary tumours . The diagnostic images and radiotherapy plans of these 12 patients were also analysed. All local recurrences occurred in the high radiation dose region (⩾70 Gy).
Results:
With a median follow-up of 40 months, OS at 2 years was 60.5%. High CD163 expression in primary tumours was associated with decreased OS (P=0.010), PFS (P=0.033), LFFS (P=0.036) and DMFS (P=0.038) in multivariate analysis. CD163 demonstrated a strong prognostic value only in human papillomavirus (p16INK4)-negative patients. Early local recurrence specimens demonstrated a significantly increased infiltration of CD11b+ myeloid cells (P=0.0097) but decreased CD31-positive vessel density (P=0.0004) compared with their matched primary samples.
Conclusions:
Altogether, baseline CD163 expression predicts for an unfavourable clinical outcome in HNSCC after definitive CRT. Early local recurrences showed increased infiltration by CD11b+ cells. These data provide important insight on the role of TAMs in mediating response to CRT in patients with HNSCC. 相似文献
We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype.
Materials and methods
Normal breast parenchyma?≥?5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44+CD49f+CD133/2+ mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples.
Results
8 of 8 IBC samples expressed isolated CD44+CD49f+CD133/2+ stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p?=?0.001). Similarly, the median number of CD44+CD49f+CD133/2+ cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p?=?0.007). 7 of 8 IBC samples expressed CD68?+?histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p?=?0.001). In the validation cohort, the median number of CD68?+?cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p?=?0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p?=?0.02) and with a 79-gene IBC signature (p?<?0.001).
Conclusions
Normal tissue from IBC patients is enriched for both mammary stem cells and macrophages and has higher association with both a tumorigenic stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or is induced by tumor warrants further investigation.
There currently is only limited knowledge on the role of tumor-specific immunity in cholangiocarcinoma.
Objective
This study evaluated the clinical implications of cytotoxic T lymphocyte antigen-4 (CTLA-4) expression levels and CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) in extrahepatic bile duct (EHBD) cancer.
Patients and Methods
Immunohistochemistry of CTLA-4, CD4, and CD8 was performed for 77 EHBD cancer patients undergoing surgery plus adjuvant chemoradiotherapy. CTLA-4 expression on tumor cells and TILs were assessed by using H-scores and the proportion of CTLA-4+ lymphocytes, respectively.
Results
With optimal cutoff values determined by a maximal chi-square method with overall survival (OS) data, patients with CTLA-4 H-score >70 and a proportion of CTLA-4+ TILs >0.15 showed higher mean density of CD8+ and CD4+ TILs, respectively (P?=?0.025 for CD8+ and P?=?0.055 for CD4+ TILs). The high CTLA-4 H-score level was associated with prolonged OS and disease-free interval (DFI) (P?=?0.025 and 0.004, respectively). With differential levels of CTLA-4 H-score according to hilar and non-hilar locations (high rate 32 vs. 68%, respectively; P?=?0.013), an exploratory subgroup analysis demonstrated that the associations between the CTLA-4 expression and OS and DFI were confined to hilar tumors (P?=?0.003 and <0.001, respectively), but not to non-hilar ones (P?=?0.613 and 0.888, respectively).
Conclusions
This study demonstrates a potential prognostic relevance of CTLA-4 expression in EHBD cancer. We suggest a differential survival impact of the CTLA-4 expression level according to different tumor locations.
Tumor-associated macrophages (TAMs) of the M2 phenotype are known to promote tumor proliferation and to be associated with a poor prognosis in numerous cancers. Here, we investigated whether M2 macrophages participate in the development of peritoneal dissemination in gastric cancer.
Methods
The characteristics of peritoneal macrophages in gastric cancer patients with or without peritoneal dissemination were examined by flow cytometry and the real-time quantitative polymerase chain reaction. The effects of M2 macrophages on phenotypic changes of the gastric cancer cell line MKN45 were assessed with a direct or indirect co-culture system in vitro and an in vivo mouse xenograft model.
Results
The number of peritoneal macrophages with the M2 phenotype (CD68+CD163+ or CD68+CD204+) was significantly higher in gastric cancer patients with peritoneal dissemination than in those without peritoneal dissemination. Higher expression of the M2-related messenger RNAs (IL-10, vascular endothelial growth factor A, vascular endothelial growth factor C, matrix metalloproteinase 1, and amphiregulin) and lower expression of M1-related messenger RNAs (TNF-α, CD80, CD86, and IL-12p40) were also confirmed in the TAMs. Macrophage co-culture with gastric cancer cells converted M1 phenotype into M2 phenotype. Moreover, the coexistence of MKN45 cells with M2 macrophages resulted in cancer cell proliferation and an acceleration of tumor growth in the xenograft model.
Conclusions
Intraperitoneal TAMs in gastric cancer patients with peritoneal dissemination were polarized to the M2 phenotype, and could contribute to tumor proliferation and progression. Therefore, intraperitoneal TAMs are expected to be a promising target in the treatment of peritoneal dissemination in gastric cancer.
Macrophages play a critical role in the initiation and progression of various solid tumors. However, their prognostic significance in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. This study investigated the distribution patterns of macrophages in PDAC and possible association with the overall survival (OS). We found significant differences in macrophage density (identified by CD68 and CD163 immunopositivity; p?<?0.001 for both) between primary cancer and paired adjacent normal tissues. Most macrophages in cancerous pancreatic tissues were located in the stroma rather than the islets (p?=?0.032 and p?<?0.001). We also demonstrated that a high total macrophage density (characterized by CD68 immunopositivity) correlated with an absence of jaundice before surgery (p?=?0.03) and that a high density of M2 macrophages (characterized by CD163 immunopositivity) in the stroma strongly correlated with the tumors located in the tail and body of the pancreas (p?=?0.04). In addition, OS was shorter in patients with high-density M2 macrophage infiltration than in those with low-density M2 macrophage infiltration (p?=?0.012). Moreover, multivariate analysis revealed that dense M2 macrophage infiltration into the stroma was an independent prognostic factor for PDAC patients (p?=?0.02). 相似文献
CD45RO is a marker for memory lymphocytes. Whether CD45RO+ tumor-infiltrating lymphocytes (TILs) prevent breast cancer recurrence is unclear.
Methods
In the present study, we evaluated CD45RO expression in TILs as a predictor of prognosis in 98 patients with breast cancer who underwent radical surgery without neoadjuvant chemotherapy. Patients were classified as CD45RO+/TILsHigh or CD45RO+/TILsLow based on median immunohistochemistry levels.
Results
CD45RO+/TILsHigh were associated with smaller tumor size. The CD45RO+/TILsHigh group also had significantly fewer metastatic lymph nodes (P = 0.0082) and fewer peritumoral lymphatic invasions (P = 0.0284). The CD45RO+/TILsHigh group enjoyed longer recurrence-free survival (P = 0.0453) but not cancer-specific survival (P = 0.0640) in univariate analysis.
Conclusions
These results suggested that CD45RO+ effector cells may both help eradicate local tumors and prevent metastases to the lymphatic systems in breast cancer patients. High ratio of CD45RO expressing TILs was associated with recurrence-free survival improvement and a trend toward cancer-specific survival improvement in breast cancer patients.
Syntenin1/SDCBP (syndecan binding protein), also known as melanoma differentiation associated gene-9 (MDA-9), is a PDZ domain-containing molecule, which was initially identified as a key oncogene in melanoma. However, the role of syntenin1 in triple-negative breast cancer (TNBC), especially in suppression of antitumour immune response, remains unknown.
Methods and Results
One hundred TNBC tissues were obtained after radical resection and used for analysis. High syntenin1 expression was associated with increased tumour size (r?=?0.421, P?<?0.001), presence of lymph node metastasis (r?=?0.221, P?=?0.044) and poor overall survival (P?=?0.01) and recurrence-free survival (P?=?0.007). Syntenin1 overexpression significantly promoted 4T1 tumour growth and lung metastasis in BALB/c mice by affecting CD8+ T cells. Western blot and flow cytometry analyses demonstrated that syntenin1 induced CD8+ T cell apoptosis in vitro and in vivo through upregulating PD-L1. Western blot demonstrated that syntenin1 upregulated PD-L1 expression by inducing Tyr705 stat3 phosphorylation, which was further confirmed by stat3 inhibition study. The correlation between syntenin1 and PD-L1 was further confirmed using tumour tissues derived from patients with TNBC (r?=?0.509, P?<?0.001). Efficacy studies indicated that 4T1-scramble tumour benefitted from anti-PD-L1 therapy (P?<?0.001); however, 4T1-syntenin1-KD demonstrated no response to anti-PD-L1 treatment (P?=?0.076).
Conclusions
Syntenin1 exhibits a profound function in mediating T cells apoptosis by upregulating PD-L1 and thus could be used as a prognostic biomarker of TNBC. Tumoural syntenin1 expression corelated with anti-PD-L1 treatment efficacy. Targeting syntenin1-mediated T-cell suppression could be a potential strategy for improving the prognosis of patients with TNBC.
Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC >2.6 in DLBCL and ALC/AMC?≥?4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p?<?0.05). In DLBCL, MVD?>?42 blood vessels/0.36 mm2 correlated with primary resistant disease (p?<?0.0001), poorer EFS and OS (p?=?0.014). High CD44s expression in FL correlated with inferior EFS and OS (p?<?0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51–7.09, p?=?0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08–1.79, p?=?0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17–23.21, p?=?0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06–14.95, p?=?0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s). 相似文献
The immune system plays a major role in cancer progression. In solid tumors, 5-40 % of the tumor mass consists of tumor-associated macrophages (TAMs) and there is usually a correlation between the number of TAMs and poor prognosis, depending on the tumor type. TAMs usually resemble M2 macrophages. Unlike M1-macrophages which have pro-inflammatory and anti-cancer functions, M2-macrophages are immunosuppressive, contribute to the matrix-remodeling, and hence favor tumor growth. The role of TAMs is not fully understood in breast cancer progression.
Methods
Macrophage infiltration (CD68) and activation status (HLA-DRIIα, CD163) were evaluated in a large cohort of human primary breast tumors (562 tissue microarray samples), by immunohistochemistry and scored by automated image analysis algorithms. Survival between groups was compared using the Kaplan-Meier life-table method and a Cox multivariate proportional hazards model. Macrophage education by breast cancer cells was assessed by ex vivo differentiation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of breast cancer cell conditioned media (MDA-MB231, MCF-7 or T47D cell lines) and M1 or M2 inducing cytokines (respectively IFN-γ, IL-4 and IL-10). Obtained macrophages were analyzed by flow cytometry (CD14, CD16, CD64, CD86, CD200R and CD163), ELISA (IL-6, IL-8, IL-10, monocyte colony stimulating factor M-CSF) and zymography (matrix metalloproteinase 9, MMP-9).
Results
Clinically, we found that high numbers of CD163+ M2-macrophages were strongly associated with fast proliferation, poor differentiation, estrogen receptor negativity and histological ductal type (p<0.001) in the studied cohort of human primary breast tumors. We demonstrated ex vivo that breast cancer cell-secreted factors modulate macrophage differentiation toward the M2 phenotype. Furthermore, the more aggressive mesenchymal-like cell line MDA-MB231, which secretes high levels of M-CSF, skews macrophages toward the more immunosuppressive M2c subtype.
Conclusions
This study demonstrates that human breast cancer cells influence macrophage differentiation and that TAM differentiation status correlates with recurrence free survival, thus further emphasizing that TAMs can similarly affect therapy efficacy and patient outcome.
Electronic supplementary material
The online version of this article (doi:10.1186/s13058-015-0621-0) contains supplementary material, which is available to authorized users. 相似文献
The infiltration of FOXP3+ regulatory T cells into invasive tumors has been reported to be associated with survival in a variety of cancers. The prognostic significance of FOXP3+ tumor-infiltrating lymphocytes (TILs) in breast cancer, however, remains controversial.
Methods
FOXP3+ TILs were assessed by immunohistochemistry on tissue microarrays constructed from a well-defined cohort of 3,992 breast cancer patients linked to detailed demographic, biomarker, treatment and outcome data. Survival analyses were performed using the Kaplan-Meier function and Cox proportional hazards regression models to evaluate the association of FOXP3+ TILs with breast cancer-specific survival, stratified by intrinsic subtype and cytotoxic T-cell infiltration status (as defined by CD8 immunohistochemistry).
Results
The presence of high numbers of FOXP3+ TILs was significantly associated with young age, high grade, estrogen receptor (ER) negativity, concurrent CD8+ cytotoxic T-cell infiltration, and human epidermal growth factor receptor-2 positive (HER2+)/ER? and core basal subtypes. On multivariate survival analysis, a high level of FOXP3+ TILs was significantly associated with poor survival in ER+ breast cancers that lacked CD8+ T-cell infiltrates (hazard ratio (HR)?=?1.30, 95% confidence interval (CI)?=?1.02 to 1.66). However, in ER? breast cancers, FOXP3+ TILs were strongly associated with improved survival in the HER2+/ER? subgroup, particularly in those with co-existent CD8+ T-cell infiltrates (HR?=?0.48, 95% CI?=?0.23 to 0.98), for which the presence of high levels of FOXP3+ TILs was independent of standard clinical prognostic factors.
Conclusions
FOXP3+ regulatory TILs are a poor prognostic indicator in ER+ breast cancer, but a favorable prognostic factor in the HER2+/ER? subtype. The prognostic value of FOXP3+ TILs in breast cancer differs depending on ER and HER2 expression status and CD8+ T-cell infiltration. 相似文献
We have previously demonstrated a significant correlative relationship between PTEN deletion and ERG rearrangement, both in the development of clinically localized prostate cancers and metastases. Herein, we evaluate the cooperative role of ERG and PTEN in oncological outcomes after radical prostatectomy for clinically localized prostate cancer. We evaluated ERG and PTEN status using three previously described cohorts. The first cohort included 235 clinically localized prostate cancer cases represented on tissue microarrays (TMA), evaluated using previously validated FISH assays for ERG and PTEN. The second cohort included 167 cases of clinically localized prostate cancer on TMAs evaluated for PTEN by FISH, and for PTEN and ERG by dual IHC. The third cohort comprised 59 clinically localized prostate cancer cases assessed by array comparative genomic hybridization (aCGH). Kaplan–Meir plots and long rank tests were used to assess the association of ERG and PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. Of the 317 cases eligible for analyses with evaluable ERG and PTEN status, 88 (27.8%) patients developed biochemical recurrence over a median follow-up of 5.7 years. Overall, 45% (142/317) of cases demonstrated ERG rearrangement and 20% (62/317) of cases demonstrated PTEN loss. Hemizygous and homozygous deletion of PTEN was seen in 10% (18/175) and 3% (5/175) of ERG-negative cases, respectively. In contrast, hemizygous and homozygous deletion of PTEN was seen in 11% (15/142) and 17% (24/123) of ERG-positive cases, respectively. PTEN loss (heterozygous or homozygous) was significantly associated with shorter time to biochemical recurrence compared to no PTEN loss (p?<?0.001). However, ERG rearrangement versus no rearrangement was not associated with time to PSA recurrence (p?=?0.15). Patients who exhibited ERG rearrangement and loss of PTEN had no significant difference in time to recurrence compared to patients with wild-type ERG and loss of PTEN (p?=?0.30). Our findings confirm a mutual cooperative role of ERG and PTEN in the pathogenesis of prostate cancer, particularly for homozygous PTEN deletion. ERG did not stratify outcome either alone or in combination with PTEN in this cohort. 相似文献
Immunologic factors can promote the progression of oral squamous cell carcinomas (oscc). The phylogenetic highly conserved protein Galectin 3 (Gal3) contributes to cell differentiation and immune homeostasis. There is evidence that Gal3 is involved in the progression of oscc and influences the regulation of macrophage polarization. Macrophage polarization (M1 vs. M2) in solid malignancies like oscc contributes to tumor immune-escape. However, the relationship between macrophage polarization and Gal3 expression in oscc is not yet understood. The current study analyzes the association between histomorphologic parameters (T-, N-, L- Pn-status, grading) and Gal3 expression resp. the ratio between Gal3 expressing cells and CD68 positive macrophages in oscc specimens.
Methods
Preoperative diagnostic biopsies (n?=?26) and tumor resection specimens (n?=?34) of T1/T2 oscc patients were immunohistochemically analyzed for Gal3 and CD68 expression. The number of Gal3 expressing cells and the ratio between CD68 and Gal3 expressing cells was quantitatively assessed.
Results
In biopsy and tumor resection specimens, the number of Gal3 positive cells as well as the Gal3/CD68 ratio were significantly (p?<?0.05) higher in T2 oscc compared to T1 cases. In biopsy specimens, a significantly (p?<?0.05) increased Gal3 expression and Gal3/CD68 ratio was associated with the progression marker lymph vessel infiltration (L1). Tumor resection specimens of cases with lymph node metastases (N+) had a significantly (p?<?0.05) increased Gal3 expression. Additionally, a high Gal3/CD68 ratio correlated significantly (p?<?0.05) with higher grading (G3) in tumor resection specimens.
Conclusion
High Gal3 expression in oscc is associated with tumor size (T-status) and parameters of malignancy (N-, L-status, grading). Gal3 might contribute to M2 macrophage mediated local immune tolerance. Gal3 expression shows association with prognosis in oscc and represent a potential therapeutic target.
Invasive micropapillary carcinoma (IMPC) is a distinct histopathological variant of breast carcinoma and frequently develops lymph node metastases. CD44 is a family of transmembrane glycoprotein receptors with multiple variant isoforms (CD44v), which have tissue-specific expression. Previous studies have demonstrated a loss or gain of CD44v and CD44 standard form (CD44s) expression in breast carcinomas. In this study, we analyzed the immunoprofiles of CD44s, CD44v6, and CD44v9 in IMPC and compared them with those in a concurrent invasive carcinoma of no special type (ICNST) component, thus clarifying the significance of CD44 expression in IMPC.
Methods
Twenty-one consecutive cases of mixed IMPC were included in this study. The expression statuses of CD44s, CD44v6, and CD44v9 in both the IMPC and ICNST components were analyzed semiquantitatively by immunohistochemistry.
Results
The immunohistochemical scores of CD44s, CD44v6, and CD44v9 were significantly decreased in the IMPC component compared to the ICNST component (p = 0.00335 for CD44s, p = 0.000982 for CD44v6, and p = 0.00271 for CD44v9). Moreover, the immunohistochemical scores of CD44v6 in the IMPC component and CD44v9 in the ICNST component of lymph node metastasis cases were significantly lower compared to cases without lymph node metastasis (p < 0.01).
Conclusions
Decreased CD44 expression may play an important role in promoting lymph node metastasis in IMPC through an inability or decreased capacity to bind with the surrounding stroma. Moreover, high CD44s+ expression levels in the concurrent ICNST component may be related to the development of IMPC.
Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial.
Methods
We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor–node–metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER+ or PR+/HER2? subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease.
Results
The clinical stage was significantly higher in the ILC patients than in the IDC (p = 0.001). The mean (±SD) of DFS for the ILC and IDC patients was 2.6 ± 0.6 and 2.4 ± 0.3 years, respectively, with no significant difference (p = 0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p = 0.05). In ER+ or PR+/HER2? subtype, the mean DFS for the ILC and IDC was 2.9 ± 0.6 and 3.1 ± 0.3 years, and the median survival time after the recurrence for ILC and IDC patients was 4.2 ± 0.7 and 5.6 ± 0.7 years, respectively, with no significant difference (p = 0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p < 0.01), while the frequency of peritoneal metastases was significantly higher in the ILC group (68.8%) than in the IDC group (1%) (p = 0.00). Of note, the prognosis after the diagnosis of peritoneal metastases was poor, with a median survival time of 19 ± 9 months and resistance to hormone therapy.
Conclusions
The extremely high rate (68.8%) of peritoneal metastases was observed in long-term follow-up for the metastatic breast cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.
The purpose of this study was to evaluate microvessel density (MVD) as assessed by C-type lectin 14A (CLEC14A), which is a new marker for endothelial cells, and compare its expression to CD31 and CD105 in epithelial ovarian cancer (EOC).
Methods
MVD was evaluated in tumors (n = 50) from patients with EOC who underwent primary surgery and in patients with EOC who received preoperative chemotherapy (n = 49) using immunohistochemistry with antibodies to CLEC14A, CD31 and CD105. The median duration of follow-up was 24.5 months (range 1?101 months). The effect of prognostic factors on event-free survival (EFS) and overall survival (OS) was assessed using the Cox regression model.
Results
The amount of residual disease was found to be an independent prognostic factor in multivariate analysis with respect to EFS (P = 0.009) and OS (P < 0.001). The mean MVD of CLEC14A (MVD = 6), in tumors from patients who underwent primary surgery, was significantly lower than that of CD31 (MVD = 25, P < 0.0001) and CD105 (MVD = 11, P = 0.018). However, there was no significant correlation between MVD as detected by these markers and clinical outcome. There was no expression of CLEC14A in tumors from patients who received preoperative chemotherapy and the MVD of CD31 and CD105 was significantly reduced (P = 0.001 and 0.006, respectively) in this set of patients.
Conclusion
This study demonstrates MVD as detected by CLEC14A in EOC. Treatment with chemotherapy reduces tumor blood vessels significantly. We suggest that CLEC14A may be a more specific endothelial marker to assess tumor angiogenesis.
The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients.
Methods
Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations.
Results
The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176).
Conclusions
Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.
Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC.
Methods.
We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors.
Results.
The median age was 50 years (range, 24–83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER+ patients, 73.5% for ER+HER-2+ patients, 54.0% for HER=2+ patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001–.03).
Conclusions.
TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype. 相似文献
