Peritumoral Inflammatory Infiltrate Research Articles

Prognostic significance of poorly differentiated clusters and tumor budding in colorectal liver metastases.

Histomorphological features have been described as prognostic factors after resection of colorectal liver metastases (CLM). The objectives of this study were to assess the prognostic significance of tumor budding (TB) and poorly differentiated clusters (PDC) among CLM, and their association with other prognostic factors. We evaluated 229 patients who underwent a first resection of CLM. Slides stained by HE were assessed for TB, PDC, tumor border pattern, peritumoral pseudocapsule, peritumoral, and intratumoral inflammatory infiltrate. Lymphatic and portal invasion were evaluated through D2-40 and CD34 antibody. Factors independently associated with poor overall survival were nodules>4 (P = 0.002), presence of PDC G3 (P = 0.007), portal invasion (P = 0.005), and absence of tumor pseudocapsule (P = 0.006). Factors independently associated with disease-free survival included number of nodules>4 (P < 0.001), presence of PDC G3 (P = 0.005), infiltrative border (P = 0.031), portal invasion (P = 0.006), and absent/mild peritumoral inflammatory infiltrate (P = 0.002). PDC and TB were also associated with histological factors, as portal invasion (TB), peritumoral inflammatory infiltration (PDC), infiltrative border, and absence of tumor pseudocapsule (TB and PDC). This is the first study demonstrating PDC as a prognostic factor in CLM. TB was also a prognostic factor, but it was not an independent predictor of survival.

Ex vivo confocal microscopy features of cutaneous squamous cell carcinoma.

Rapid microscopic evaluation of cutaneous squamous cell carcinoma (SCC), its grade of differentiation and level of invasiveness would enable better management of patients' therapy. Analyzing specific ex vivo confocal microscopy criteria whether they can predict diagnosis of invasive SCC vs carcinoma in situ and poorly differentiated or undifferentiated vs well and moderately differentiated SCC. Ex vivo confocal images of 102 SCCs in 57 patients were evaluated immediately after excision for the presence of predefined criteria based on confocal and histological knowledge. In histopathological examination, 30 SCCs were in situ and 72 invasive. Of these, 29 invasive SCC tumors were well, 19 moderately, 15 poorly differentiated and 9 undifferentiated. χ2 analysis demonstrated that presence of erosion/ulceration, plump bright or speckled cells in dermis, keratin pearls and peritumoral inflammatory infiltrate correlated with diagnosis of invasive SCC. Erosion/ulceration and peritumoral inflammatory infiltrate were observed more frequently in poorly differentiated or undifferentiated tumors. Plump bright or speckled cells in the dermis were observed less often in well-differentiated tumors. The presence of keratin pearls was associated with well or moderately differentiated tumors. Ex vivo CLSM allowed rapid examination of SCC and provided useful information on invasiveness and grading of the tumor.

Indoleamine 2,3-Dioxygenase Expression in Primary Cutaneous Melanoma Correlates with Breslow Thickness and Is of Significant Prognostic Value for Progression-Free Survival

The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO inhibitors were added to the regimen. Data on IDO expression in primary human melanomas are, however, incomplete and conflicting. Here, we show that the level of IDO expression in primary human melanoma cells significantly correlates with Breslow thickness (P=0.003), the presence of tumor-infiltrating lymphocytes (P= 0.029), and the intensity of the peritumoral inflammatory infiltrate (P= 0.001). The expression of IDO in melanoma cells predicted independently of Breslow thickness and tumor stage (P= 0.04). We further show that CD11c+ dendritic cells and CD68+ macrophages in the microenvironment of melanomas express IDO. The level of IDO expression in antigen-presenting cells correlated positively to peritumoral inflammation (P= 0.001) but not to tumor-infiltrating lymphocytes. Significant negative correlation with progression-free survival was found for patients for whom antigen-presenting cells were very strongly IDO positive. These results suggest that IDO induction within melanoma cells may directly reflect tumor progression, whereas IDO in antigen-presenting cells may determine immune surveillance with impact on local and systemic tolerance.

Study of peritumoral inflammatory infiltrate density in kidney cancer: prognostic significance

Study of peritumoral inflammatory infiltrate density in kidney cancer: prognostic significance

Prognostic significance of evaluation of peritumoral inflammatory infiltrate density in kidney cancer

Prognostic significance of evaluation of peritumoral inflammatory infiltrate density in kidney cancer

Programmed death ligand-1 (PD-L1) expression in penile squamous cell carcinoma.

393 Background: PD-1 protein is a co-inhibitory receptor expressed on B cells, T cell, and NK cells. Its ligand PD-L1 (B7-H1) leads to inhibition of T cell proliferation and cytokine production and is not expressed on normal tissues other than macrophages, but is expressed on various human carcinomas. Expression of PD-L1 in the HPV-associated disease penile carcinoma is unknown. Methods: Formalin-fixed paraffin-embedded tumor specimens were obtained from 19 patients. PD-L1 staining was done with an E1L3N rabbit monoclonal antibody with the summary of a positive score using H-score membrane staining, which considers both intensity and percentage of cells, with &gt;5% score as a positive. HPV status was also evaluated using FISH or p16 immunohistochemical staining to evaluate for correlation with PD-L1. Results: 23 samples between primaries and lymph nodes were collected from the 19 patients with 5/23 samples (22%) positive for anti-PDL1 staining. 6 samples (26%) were positive for HPV by at least one method of testing with 2/6 (33%) HPV positive patients having positive PD-L1 membrane staining. In both of these samples, there was equivocal peritumoral inflammatory infiltration of PD-L1 cells. Conclusions: This analysis shows that PD-L1 is expressed in penile squamous cell carcinomas and may indicate a role for future anti-PD-L1/PD-1 drugs as therapeutic options. Further analyses of correlated clinical features, survival, and separate PD-L1 staining in peritumoral inflammatory cells are underway.

Changes in the inflammatory microenvironment in premalignant colonic adenomatous polyps: Evidence for immunosurveillance?

535 Background: The majority of colorectal cancers develop through the adenoma-carcinoma sequence. Recently, the host inflammatory response has become recognized as a key determinant of outcome. In particular, a pronounced peri-tumoral local inflammatory infiltrate identifies those with a better outcome. The present study aimed to characterize the local inflammatory response in pre-malignant colorectal adenomatous polyps. Methods: Patients with adenomatous polyps removed at colonoscopy as part of a population FOBt screening program were identified from a prospectively maintained database. All polyps were greater than 1cm. Whole slide immunohistochemistry was performed to assess intraepithelial T-cell (CD3+), cytotoxic T-cell (CD8+) and macrophage (CD68+) infiltrate. Inter-observer agreement for assessment of inflammatory cell infiltrate was good or better for CD3+, CD8+ and CD68+staining (Kappa 0.66, 0.66, 0.79 respectively). Results: A total of 207 adenomatous polyps, 107 high-grade (HG), 100 low-grade (LG), from 134 patients were included. Median age was 65 years, 33 (25%) were female and 15 (11%) were taking regular aspirin. Comparing HG and LG polyps, there were more older and female patients in the HG group (p&lt;0.05). There was no difference in location (p=0.222), macroscopic morphology (p=0.445) or aspirin (p=0.377) use between groups. Microscopically, HG polyps were more likely to contain a villous component than LG polyps (65% vs 50%, p&lt;0.05). Overall, high levels of CD3+, CD8+ and CD68+ infiltrate were observed in 68%, 25% and 72% of polyps respectively. Both CD3+ (74% vs 61%, p&lt;0.05) and CD8+ (37% vs 13%, p&lt;0.001) infiltrate was higher in HG polyps compared to LG polyps. There was no association with polyp grade and CD68+infiltrate (74% vs 70%, p=0.540). Conclusions: An increase in local T-lymphocytic infiltrate, but not macrophage infiltrate was identified with progression from low-grade to high-grade dysplasia. This would suggest a specific response to early disease progression confirming increased immunosurveillance. Therefore, such early stage disease may amenable to immunomodulatory treatment.

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma.

BackgroundSquamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness.MethodsTo extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models.ResultsWe found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively.ConclusionsTaken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.

N-acetylglucosaminidase, myeloperoxidase and vascular endothelial growth factor serum levels in breast cancer patients

Inflammatory cells surround breast carcinomas and may act promoting tumor development or stimulating anti-tumor immunity. N-acetylglucosaminidase (NAG) has been employed to detect macrophage accumulation/activation. Myeloperoxidase (MPO) is considered a marker for neutrophils activity/accumulation. Vascular Endothelial Growth Factor (VEGF) is as strong pro-angiogenic cytokine. The aim of this study was to measure the systemic inflammatory response by measuring serum levels of NAG, MPO and VEGF in women diagnosed with breast cancer and associate this response to the peritumoral inflammatory infiltrate and to prognostic factors. Serum samples obtained from women with no evidence of disease (n=31) and with breast cancer (n=68) were analyzed for the activities of NAG, MPO and VEGF by enzymatic assay. Serum levels of NAG and VEGF were higher in healthy volunteers (P<0.0001) and serum levels of MPO were higher in patients with breast cancer (P=0.002). Serum levels of NAG were positively correlated to serum levels of MPO and VEGF (P<0.0001 and P=0.0012, respectively) and MPO and VEGF serum levels had also a positive correlation (P=0.0018). The inflammatory infiltrate was not associated to serum levels of the inflammatory markers, and higher levels of MPO were associated to lymphovascular invasion negativity (P=0.0175).

Tumour Src kinase family member expression correlates with peritumoral inflammatory cell infiltrate in a cohort of early breast cancer patients

Tumour Src kinase family member expression correlates with peritumoral inflammatory cell infiltrate in a cohort of early breast cancer patients

Macrophage migration inhibitory factor and oral cancer

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with pro-inflammatory functions and involved in tumorigenesis. The aim of this study was to evaluate the expression and localization of the macrophage MIF in oral squamous carcinoma (OSC). In addition, the relationship between MIF expression and clinicopathological parameters such as survival data, tobacco use, alcohol habits, TNM stage, tumor graduation, and peritumoral inflammatory infiltrate were evaluated. Using immunohistochemistry, expression and localization of MIF was detected in 44 specimens of OSC. The absolute number and relative proportions of MIF-positive cells detected were also determined separately for tumor parenchyma vs. stroma. All counts were determined from 10 consecutive high-power fields using an integration graticule. Moreover, some parameters were analyzed separately for lip and intra-oral cancers. Migration inhibitory factor-positive cells were observed in both the tumor parenchyma and in inflammatory cells of all specimens. In contrast, MIF expression was not detected in tumoral nests associated with poorly differentiated tumors. In specimens of lip cancer, a greater number of MIF-positive stromal immune cells were detected than in intra-oral cancer specimens (Mann-Whitney test, P = 0.049). Oral squamous carcinoma cells consistently express MIF independent of their location. Lip tumors presented more MIF-positive peritumoral inflammatory cells, similar to control, suggesting that immunological differences in leukocyte activation exist between in lip and intra-oral cancers.

Serum MMP‐8 levels increase in colorectal cancer and correlate with disease course and inflammatory properties of primary tumors

Matrix metalloproteinases (MMPs) form a family of zinc-dependent endoproteases participating in cancer pathogenesis by promoting invasion and regulating growth signaling, apoptosis, angiogenesis and immune responses. MMP-8 is an intriguing MMP with recently discovered antitumor activity and immunoregulatory properties, but its role in colorectal cancer (CRC) has not been studied extensively. Preoperative serum MMP-8 levels (S-MMP-8) of 148 CRC patients and 83 healthy controls were measured using an immunofluorometric assay and related to clinical and pathological parameters. The patients had higher S-MMP-8 than the controls (median 63.0 vs. 17.2 ng/ml, p = 1.5E - 9), and a receiver operating characteristics analysis yielded an area under the curve of 0.751 in differentiating the groups. In univariate analyses, S-MMP-8 correlated positively with disease stage (p = 4.5E - 4), the degree of primary tumor necrosis (p = 0.0024) and blood neutrophil count (Pearson r = 0.523, p = 2.5E - 9). Particular interest was also addressed to the inflammatory properties of the tumors, and both variables studied, peritumoral tumor-destructing inflammatory infiltrate and Crohn's-like lymphoid reaction (CLR), showed a negative correlation with S-MMP-8 (p = 0.041 and p = 0.0057, respectively). In a multiple linear regression analysis, high S-MMP-8 associated with elevated blood neutrophil count, distant metastases, low-grade CLR and low body mass index. Overall, our results indicate that MMP-8 is involved in the course and progression of CRC influencing the immune response against the tumor and contributing to the resolution of necrosis. Serum or plasma MMP-8 may prove to be a worthy biomarker for CRC.

Facial basal cell carcinoma: Analysis of recurrence and follow-up strategies

Rates of recurrence after incomplete surgical excision of basal cell carcinoma (BCC) range from 4 to 16.6% of analyzed cases. The aim of the present study was to identify the predictive factors associated with facial BBC recurrence following excision and their influences, in order to establish a proper therapeutic strategy. A monocentric retrospective study was performed reviewing all BCCs surgically excised at the Institute of Plastic Surgery, University of Padua, with particular focus on the involvement of surgical margins and recurrence. Seven hundred and nineteen lesions in 605 patients were studied. Correlations between recurrence probability and various characteristics of BCC were analyzed using a logistic regression model. It was observed that incomplete excision, deep margin involvement, the presence of sclerodermiform or metatypic basaloid squamous cells, as well as pleomorphous histological variants and/or peritumoral inflammatory infiltrates, were all related to an increase in the probability of recurrence. BCC excision must be followed by individualized management with particular consideration for the localization, the histological type and other known predisposing factors; the treatment strategy and, in particular, the length of the surveillance period and the frequency of patient assessment should be evaluated on the basis of the recurrence probability outlined.

Peri-Tumoral Inflammatory Cell Infiltration in OSCC: A Reliable Marker of Local Recurrence and Prognosis? An Investigation Using Artificial Neural Networks

The presence of inflammatory reaction in peri-tumoural connective tissue is generally considered as a defense mechanism against cancer, but inflammation tissue in malignant transformation and early steps of oncogenesis has been recently proven to play a supporting and aggravating role in some carcinomas. Aims of this retrospective study were to evaluate in OSCCs the independent association of peri-tumoral inflammatory infiltrate (PTI) with local recurrence (LR) or survival outcome, and to verify whether PTI can be considered a marker of prognosis. Data from 211 cases of OSCC, only surgically treated between 1990 and 2000, were collected and retrospectively analyzed for PTI and the event LR (5 yrs follow-up at least) by means of univariate-multivariate and neural networks analyses. Patients (mean age 65.3 ± 12.4 yrs, M/F = 2.98) showed presence of PTI in 68.2% (144/211): (+) in 27.0%, (++) in 25.6%, (+++) 15.6%; PTI was found reduced in 24.7% of cases and absent in 7.1%. In overall PTI+ve group (n=144), 66 were TNM Stage I, 33 Stage II, 45 Stage III, none Stage IV. LR (mean 6 ± 4 months) was present in 87/211 (41.2%) patients, of which 43/144 (29.8%) in OSCCs with PTI [23 (+), 13 (++) and 7 (+++)] vs. 44/67 (65.7%) in OSCC with PTI -/+ or PTI-ve ones. By univariate analysis, PTI+ve cases showed a significant lower risk to have LR (p <0.0001; OR= 0.2297; CI= 0.1277:0.4134) vs PTI -/+ or -ve ones, especially among cases with higher PTI value (+++) (OR= 0.1718; CI= 0.0749:0.3939). Multivariate analyses (Logit model and neural networks) confirmed the same datum: presence of PTI was an independent predictive variable accounting for a better tumoural outcome without LR (Logit and neural networks values: OR' 0.226; CI= 0.113:0.454; ROC Area = 0.66, respectively). In terms of prognostic significance, elevated PTI was found to have an independent association with the poorest overall survival rate (P = 0.056). Our findings strongly suggest the importance to investigate routinely PTI in OSCCs, as useful marker of tumoral behavior and prognosis, and warrant further studies.

A precocidade diagnóstica do melanoma cutâneo: uma observação no sul do Brasil

The incidence of melanoma cutaneous and the mortalities rates are rising in most countries worldwide. to describe the histopathological characteristics of cutaneous melanoma, according to the criteria established by the Brazilian Group of Melanoma, and to evaluate early diagnosis in a cancer treatment referral center. we performed a cross-sectional descriptive study of cases of primary cutaneous melanoma identified after excisional biopsy and processed at the pathology laboratory of Complexo Hospitalar Santa Casa between Jan 1st 2000 and Jan 15th 2005. The following variables were analyzed: age, gender, topography, histopathologic subtype, Breslow thickness, growth phase, Clark level, mitotic index, peritumoral and intratumoral lymphocytic inflammatory infiltrate, angiolymphatic invasion, ulceration, regression, type of regression, microscopic satellitosis, and surgical margins. 328 cases, 57% female and 43% male, were analyzed. Mean age was 55.6 years. For women, the most common tumor location was in inferior(29.26%) and superior limbs(23.94%), while for men melanoma was mainly found in the back(35%), followed by anterior chest/abdomen(14.29%) (p<0.05). Prevalence of histologic subtypes was the following: superficial spreading melanoma(62.8%), lentigo maligna(14.9%), nodular(14.6%), acral(7.3%), and desmoplastic(0.3%) types. Regarding Breslow, 26.2% were in situ, 36.9% had <1 mm, and only 15.9% were ? 4mm in depth. the distribution of histopathologic subtypes, as well as Breslow thickness, was in accordance with previous studies in outpatient populations. The profile of cases of cutaneous melanoma diagnosed in a tertiary hospital seems to be experiencing some changes over the last two decades, with a current trend for earlier diagnosis.

Double-blind Placebo-controlled Study With Interleukin-18 and Interleukin-12-encoding Plasmid DNA Shows Antitumor Effect in Metastatic Melanoma in Gray Horses

Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmid DNA, interleukin-12-encoding plasmid DNA, or empty plasmid DNA (control group), injected intratumorally, respectively. Tumor response was assessed using ultrasound and caliper measurements and histologic assessment of tumor biopsies. Significant tumor regression could be shown in both the treatment groups receiving IL-18 and IL-12-encoding plasmid DNA whereas placebo-treated control patients showed tumor growth over the course of the treatment. In addition, 7 of 10 tumors from horses treated with IL-18 or IL-12 showed peritumoral and/or intratumoral inflammatory infiltrates after treatment compared with 1 of the 6 in the control group. The treatment as assessed by serial blood draws and clinical investigation, was safe and well tolerated. These data suggest that the intratumoral treatment with IL-18 and IL-12-encoding plasmid DNA has antitumor effects, which is well tolerated and thus holds promise for the treatment of patients with metastatic melanoma.

Endometrial Giant Cell Carcinoma: A Case Series and Review of the Spectrum of Endometrial Neoplasms Containing Giant Cells

Poorly differentiated endometrial carcinomas of specific type include the rarely reported endometrial carcinoma with a malignant giant cell component [endometrial giant cell carcinoma (GCC)]. Since the initial description in 1991, there has only been 1 subsequent case report of this entity. We report another 5 cases. The patients ranged in age from 53 to 83 years, presenting with vaginal bleeding, anemia, or a pelvic mass. Four of the 5 tumors contained areas of endometrial adenocarcinoma of usual type, with a variable giant cell component. The conventional cell types present included 1 case with clear cell carcinoma (30% of tumor volume), 2 with high-grade endometrioid carcinoma (50% and 70% of tumor volume, respectively) and 1 with serous histology (10% of tumor volume). One was composed exclusively of giant cell carcinoma. The giant cell component in all cases consisted of poorly cohesive nests of bizarre multinucleated giant cells with mononuclear tumor cells. A striking peritumoral and intratumoral inflammatory cell infiltrate composed of lymphocytes, plasma cells and focal eosinophils, and neutrophils was present and emperipolesis was noted in 4 of the 5 cases. The giant cells showed focal staining for epithelial markers (AE1/AE3 and CAM 5.2). Three of the patients presented with stage 1A disease, 1 with stage 1B disease, and 1 tumor was advanced, presenting as stage IIIC2. One patient in whom the tumor was exclusively of the giant cell type, developed lung metastasis 4 years after diagnosis and 1 patient is disease free after 14 years. The remaining 3 patients showed no evidence of disease with 15 to 32 months of follow-up. As histotype supplemented by staging information is critical in selection of treatment modalities and in prognostication in uterine malignancies, accurate classification is mandated. Here, we present a series of endometrial carcinomas containing a component of GCC and discuss the spectrum of giant cell-containing uterine neoplasms. At this time, however, the cumulative data on endometrial GCC are limited and the prognostic significance of the presence and the extent of a giant cell component in endometrial carcinoma remains uncertain.

Role of methylation of the hMLH1 gene promoter in the development of gastric and colorectal carcinoma in the elderly

The occurrence of malignant neoplasms increases with advancing age. Although aging and carcinogenesis are basically different processes, they share phenomena such as the accumulation of DNA damage and abnormal proteins. Recent advances in molecular biology have shown an accumulation of genetic and epigenetic changes in both aging and carcinogenesis, as well as the alteration of metabolism, immunosenescence and shortened telomeres. DNA methylation is a representative epigenetic phenomenon and is frequently involved in controlling gene functions during development and tumorigenesis. We herein focused on methylation of genes in the development of gastrointestinal carcinomas in the elderly. The proportion of gastric and colorectal carcinomas with hypermethylation of the hMLH1 promoter increases with age, reaching 25-30% of all carcinomas of the stomach and large intestine in elderly patients. These tumors have clinicopathological and molecular characteristics such as loss of hMLH1 expression, microsatellite instability, poorly differentiated histology, peritumoral inflammatory cell infiltration, low incidence of lymph node metastasis and favorable prognosis. However, methylation-related carcinogenesis accounts for up to approximately one-third of tumors, and other mechanisms; for example chromosomal instability as a result of telomere dysfunction, are responsible for the development of most carcinomas in the elderly.

Distinctive clinical and microscopic features of squamous cell carcinoma of oral cavity and lip

This study was undertaken to gain insight into the distinctive features of squamous cell carcinoma of the lip (LSCC) and oral cavity (OCSCC). A total of 37 cases of LSCC and 54 of OCSCC were compared regarding clinical and microscopic findings. Predominance of head and neck TNM stages (HNTNM) T1-T2 in LSCC and T3-T4 in OCSCC was observed. A significant percentage (33.3%) of patients with OCSCC at HNTNM T1-T2 presented cervical lymph node metastasis and 18.75% died, whereas lymph node metastasis was absent and no patient died with LSCC at HNTNM T1-T2. LSCC demonstrated a higher number of cases with intense peritumoral inflammatory infiltrate compared with OCSCC. The analysis of the proliferative index demonstrated a significantly higher percentage of PCNA+ and Ki-67+ cells in OCSCC compared with LSCC. Our results suggest that OCSCC and LSCC demonstrate distinct clinical and microscopic characteristics that reflect different biologic behavior and prognosis.

Comparison of Synchrotron Images of DCIS of the Breast with Their Pathologic Findings.

Abstract Background: Synchrotron radiation x-ray imaging have opened a new door to explore breast tissue below the micron scale providing detailed internal structures of the samples with a great magnification and an excellent resolution. Using phase contrast technique, we got monochromated synchrotron images of DCIS (Ductal Carcinoma In Situ) of the breast tissue section. To figure out relation with their optical microscopic features, we compared the synchrotron images of the DCIS with their histopathologic findings of the same stained section.Material and Methods: A x-ray microscope was installed on 1B2 beamline of Pohang Light Source, a third generation synchrotron radiation facility with operating energy of 2.5 GeV in Pohang, Korea. The x-ray energy was set at 11.1 keV, and the x-ray beam was monochromatized by a W/B4C monochromator. Zernike phase-shifter was adapted for phase contrast x-ray microscopy. Formalin-fixed 5µm-thick breast tissue sample was attached onto the Kapton film, and positioned 25 m away from the beam source. The synchrotron image of sample was converted into a visual image on the CsI(TI) scintillation crystal, and this visual image was captured by a full frame CCD camera. After scanning, we patched these images one and another to show the large area of the tissue section. For the comparative analysis with their synchrotron image, synchrotron-scanned breast tissue sections were stained, and the histopathologic findings of the samples were captured by image analyzer. The magnifying power of this microscope was 100x.Results: The monochromated x-ray microscopic images of DCIS of the breast tissue were obtained with a good resolution. These images revealed various structures of DCIS lesion with a good contrast and high visibility by phase contrast technique. They include prominent and intact periductal basement membrane - a hallmark of DCIS lesion, and stippled fine microcalcifications which were indistinct in the histologic section, and a shadow of intense peritumoral inflammatory cell infiltration. But the minute changes of each cancer cell showing the features of cancer tissue such as, cellular differentiation and nuclear grade, were not identified well.Discussion: The x-ray microscopic imaging of DCIS of the breast tissue section with synchrotron radiation showed a good correspondence with the histopathologic findings of their stained tissue sections. And the synchrotron image of DCIS had some unique radiologic features differentiating from histopathogic findings. Therefore the synchrotron images of the DCIS lesion appear to have a new possibility of use for the clinical and research purposes in near future. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5015.