Normal Glandular Tissue Research Articles

Detection of invasive ductal carcinoma by electrical impedance spectroscopy implementing gaussian relaxation-time distribution (EIS-GRTD)

Breast cancer detection and differentiation of breast tissues are critical for accurate diagnosis and treatment planning. This study addresses the challenge of distinguishing between invasive ductal carcinoma (IDC), normal glandular breast tissues (nGBT), and adipose tissue using electrical impedance spectroscopy combined with Gaussian relaxation-time distribution (EIS-GRTD). The primary objective is to investigate the relaxation-time characteristics of these tissues and their potential to differentiate between normal and abnormal breast tissues. We applied a single-point EIS-GRTD measurement to ten mastectomy specimens across a frequency range f = 4 Hz to 5 MHz. The method calculates the differential ratio of the relaxation-time distribution function Δγ between IDC and nGBT, which is denoted by ΔγIDC−nGBT, and Δγ between IDC and adipose tissues, which is denoted by ΔγIDC−adipose. As a result, the differential ratio of Δγ between IDC and nGBT ΔγIDC−nGBT is 0.36, and between IDC and adipose ΔγIDC−adipose is 0.27, which included in the α -dispersion at τpeak1=0.033±0.001s. In all specimens, the relaxation-time distribution function γ of IDC γIDC is higher, and there is no intersection with γ of nGBT γnGBT and adipose γadipose. The difference in γ suggests potential variations in relaxation properties at the molecular or structural level within each breast tissue that contribute to the overall relaxation response. The average mean percentage error δ for IDC, nGBT, and adipose tissues are 5.90%, 6.33%, and 8.07%, respectively, demonstrating the model’s accuracy and reliability. This study provides novel insights into the use of relaxation-time characteristic for differentiating breast tissue types, offering potential advancements in diagnosis methods. Future research will focus on correlating EIS-GRTD finding with pathological results from the same test sites to further validate the method’s efficacy.

Reference Range of CT Value in NC-CBBCT Based on Female Breast Structure.

As a new high-resolution three-dimensional CT imaging technology, the essential reference range of CT values in Cone-beam breast computed tomography (CBBCT) has not been established to date. To determine the reference range of computed tomography (CT) values in CBBCT for clinical breast examination. In total, 913 cases (1167 lateral) were subject to CBBCT. CT values of the glandular tissue, fat and different quadrants and different distances of CBBCT images were analyzed. The nipple and muscle were also evaluated. A total of 672 lateral breasts were included in the normal group for investigation. The reference range of the absolute CT value of the chest wall muscle is -136.68~43.36 HU. The reference range of the absolute CT value of the nipple is 176.39~334.02 HU. The reference range of the absolute CT value of fat is -190.4~-63.67HU, and of glandular tissue is -12.2~199.07HU. Our results firstly established the baseline CT values of Non-contrast CBBCT in female breasts, which will benefit cancer screening and lesion locating. The closer the normal breast fat and glandular tissue is to the nipple, the greater the CT value. The older the age, the lower the density. The CT values of fat are unstable in a distance of less than 5 cm, and the CT values of glandular tissues are relatively stable. The difference between the upper and lower quadrants is significant in the same lateral breast and the same section.

420 Parathyroid surgery outcomes - 2 surgeons outcomes for the past 9 years in a teaching hospital

Abstract Aim The success of parathyroid surgery in hyperparathyroidism is defined by the sustained improvement in calcium levels without the need for re-exploration. Reoperation rate in the United Kingdom currently sits at 1.6%. It has been shown that the need for repeat parathyroid surgery is related to surgeon annual volume. We aimed to review the outcomes of parathyroid surgery for hyperparathyroidism performed by two upper gastrointestinal surgeons experienced in parathyroidectomies. Methods Retrospective review of consecutive parathyroidectomy cases performed by VS and PT in a teaching hospital was conducted between April 2013 and December 2022. Data was obtained from local hospital database. Primary outcome was re-exploration within one year of index procedure. Secondary outcomes included methylene blue uptake by adenomas and postoperative vocal cord palsy. Results 211 parathyroidectomies were performed during the study period. Patient cohort was predominantly female (n=153, 72.2%). Mean age of study population was 57±13 years. Histopathology confirmed 171 (81.0%) parathyroid adenomas, 34 (16.1%) multiglandular hyperplasia and 6 (2.8%) normal glandular tissue. None were malignant adenoma. 4 (1.9%) patients required re-exploration within one year of index procedure, three of which were found to be ectopic adenomas. Preoperative methylene blue infusion was used in all cases to assist identification of adenoma; uptake was evident in 169 (80.1%) cases. 2 (0.9%) patients developed permanent recurrent laryngeal nerve damage, resulting in mild voice hoarseness. Conclusion Our dedicated parathyroid service led by experienced surgeons was associated with comparable re-exploration rates and high cure rates. Preoperative methylene blue infusion helps in intraoperative identification of parathyroid glands.

Effects of hepatocyte growth factor on porcine mammary cell growth and senescence.

The porcine mammary glands share morphological and physiological similarities with human ones, making primary porcine mammary cells (PMC) suitable for biomedical research and a potential cellular therapeutic for breast cancer xenogeneic cell immunotherapy. Primary cells isolated from tissues remain the physiological functions of origin tissues but their self-renewal ability is restricted and cells acquire senescence during in vitro expansion. To overcome these drawbacks, here we sought to establish an approach to efficiently increase PMC's in vitro growth. We studied the effects of the hepatocyte growth factor (HGF) to maintain the expansion capacity of porcine mammary cells and identify the possible mechanisms. HGF could allow for the increase in vitro proliferation capacity of primary epithelial cells isolated from tissue samples. To effectively produce cells for biomedical research and xenogeneic cell therapy, we planned to study the effects of HGF and its potential mechanisms of action to stimulate cell growth for PMC expansion. After HGF treatment, the growth, cell cycle, senescence and the cell marker gene expression of PMCs were analyzed in standard 10% FBS and low serum 1% FBS containing medium. HGF significantly enhanced the cell proliferation by shifting the cell cycle population from G1 phase into S phase to increase cell division, reduced the senescent cells and reprogrammed gene expression profiles. We demonstrated that HGF could maintain the expansion capacity of PMCs by increasing cell growth and anti-senescence capability, suggesting its potential application in optimizing the long-term culture of primary cells. Adding a specific growth factor such as HGF in culture allows enhanced expansion of heterogeneous cell populations from normal porcine mammary glandular tissues in vitro. We believe that this cell culture approach will efficiently provide cells for studying mammary cell function and supply cells for therapeutic uses.

Immunohistochemical comparative analysis of tumor stem cell biomarkers in pleomorphic adenoma, adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands

This study aimed to compare the immunoexpression profile of tumor stem cell (TSC) biomarkers CD44, aldehyde dehydrogenase 1 (ALDH1), OCT4, and SOX2 in salivary gland tumors (SGTs). Sixty tissue specimens of SGTs, including 20 pleomorphic adenomas, 20 adenoid cystic carcinomas (ACCs), and 20 mucoepidermoid carcinomas, in addition to 4 samples of normal glandular tissue, were subjected to immunohistochemistry. The expression of the biomarkers in the parenchyma and stroma was evaluated. Data were analyzed statistically by nonparametric tests (P < .05). Higher parenchymal expression of ALDH1, OCT4, and SOX2 was observed in pleomorphic adenomas, ACCs, and mucoepidermoid carcinomas, respectively. Most ACCs did not express ALDH1. Higher immunoexpression of ALDH1 in major SGTs (P = .021) and of OCT4 in minor SGTs (P = .011) was found. Immunoexpression of SOX2 was related to lesions without myoepithelial differentiation (P < .001) and malignant behavior (P = .002). Furthermore, OCT4 was related to myoepithelial differentiation (P = .009). CD44 expression was related to a better prognosis. Stromal immunoexpressions of CD44, ALDH1, and OCT4 were higher in malignant SGTs. Our findings suggest the participation of TSCs in the pathogenesis of SGTs. We emphasize the need for further investigations into the presence and role of TSCs in the stroma of these lesions.

Differentiation of Benign and Malignant Breast Lesions Using ADC Values and ADC Ratio in Breast MRI.

Magnetic resonance imaging (MRI) of the breast has been increasingly used for the detailed evaluation of breast lesions. Diffusion-weighted imaging (DWI) gives additional information for the lesions based on tissue cellularity. The aim of our study was to evaluate the possibilities of DWI, apparent diffusion coefficient (ADC) value and ADC ratio (the ratio between the ADC of the lesion and the ADC of normal glandular tissue) to differentiate benign from malignant breast lesions. Materials and methods: Eighty-seven patients with solid breast lesions (52 malignant and 35 benign) were examined on a 1.5 T MR scanner before histopathological evaluation. ADC values and ADC ratios were calculated. Results: The ADC values in the group with malignant tumors were significantly lower (mean 0.88 ± 0.15 × 10−3 mm2/s) in comparison with the group with benign lesions (mean 1.52 ± 0.23 × 10−3 mm2/s). A significantly lower ADC ratio was observed in the patients with malignant tumors (mean 0.66 ± 0.13) versus the patients with benign lesions (mean 1.12 ± 0.23). The cut-off point of the ADC value for differentiating malignant from benign breast tumors was 1.11 × 10−3 mm2/s with a sensitivity of 94.23%, specificity of 94.29%, and diagnostic accuracy of 98%, and an ADC ratio of ≤0.87 with a sensitivity of 94.23%, specificity of 91.43%, and a diagnostic accuracy of 95%. Conclusion: According to the results from our study DWI, ADC values and ADC ratio proved to be valuable additional techniques with high sensitivity and specificity for distinguishing benign from malignant breast lesions.

Primary lymphedema of breast, a case report.

IntroductionLymphedema affects the extremities of breast cancer patients post-surgical or radiation therapy. This study aims to report a case of primary lymphedema of breast.Case presentationA 41-year-old female presented with right breast swelling. It associated with hotness and intermittent mastalgia for the past 8 years. Ultrasound (US) examination showed diffuse trabeculate, skin thickening and edematous with normal glandular tissue. Magnetic resonance imaging (MRI) showed diffuse homogeneous parenchymal enhancements with diffuse tranecular and skin edema (high signal on Short-TI Inversion Recovery (STIR)). The result of the biopsy showed normal breast tissue and lymph node.DiscussionThe major risk factors of lymphedema are breast cancer surgery, radiation therapy, axillary lymph node dissection, length and location of breast incision, taking biopsy, trauma, wound infection. Forearm is the most common site of swelling. Primary lymphedema of the breast is a very rare condition without a known risk factor.ConclusionAlthough it is rare, primary lymphedema can affect the breast. US and MRI are necessary to exclude other pathologies. It is managed conservatively.

Ultrastructural study of the lacrimal glands in severe dry eye disease following Stevens-Johnson syndrome

PurposeThis study aimed to examine the ultrastructural features of the lacrimal glands of patients with severe dry eye due to Stevens-Johnson syndrome (SJS). MethodsBiopsies form orbital lobes of six lacrimal glands obtained from fresh body donors (n=3) and patients with SJS (n=3; absolute tear deficiency; 2-6 months of disease duration) were examined using transmission electron microscopy (TEM). ResultsOn TEM, normal lacrimal glandular tissue shows columnar acinar epithelial cells containing basally located rounded or oval euchromatic nuclei with cytoplasmic electron dense and ­moderately electron-dense secretory granules. Histologically, the lacrimal gland biopsies showed varied degree of acinar atrophy with lymphocytic infiltration in SJS patients. While on TEM, the lacrimal glands in SJS patients showed homogenous appearance of the nuclear chromatin of acinar cells with no differentiation into hetero-or euchromatin and loss of nucleoli. The cytoplasm lacked any electron dense material and showed significant loss of endoplasmic reticulum, mitochondria and Golgi bodies. The myoepithelial cells shared similar characteristics as in acinar epithelial cells along with loss of spindle shaped processes. ConclusionTransmission electron microscopy revealed ultrastructural changes in terms of nuclear composition, secretory vesicles, lysosomal vacuolation and myoepithelial cell distribution in the lacrimal glands of SJS patients.

A rare case of static bone cavity in the anterior mandibular region of a 10-year-old boy.

IntroductionStatic bone cavity (SBC) is a bone defect that develops as a result of localized pressure from tissues surrounding the mandible. It is most commonly observed in the mandibular angle of adult males caused by the submandibular gland. The condition is asymptomatic and requires no treatment. The frequency of onset is rare, especially in the anterior mandible, and SBC is extremely difficult to diagnose in children.Presentation of caseThis report is on a case of SBC in the anterior mandible of a 10-year-old boy. The condition could not be diagnosed after panoramic radiograph and Magnetic Resonance Imaging (MRI) analyses. Computed-topography (CT) imagery revealed an oval-shaped depression 6 × 5 × 3 mm in size at the lingual apex of the mandibular left lateral tooth. Diagnosing the patient was difficult and a tumor was suspected. For treatment, the tumor-like lesion was resected and the fistula in the periosteum was sutured and closed. One year later, the defect on the lingual mandibular bone had ossified and recovered.ConclusionThe incidence of SBC in children is rare and the condition is difficult to diagnose because of the small size of the lesions, however in this study, CT imagery proved to be useful. SBC was detected in the subject in early childhood, and his postoperative course suggested that the lesion developed as a result of glandular tissues herniating through the periosteum and causing compression on the mandible, which resulted in bone resorption. In other words, herniation of normal salivary glandular tissues were a cause of SBC.

Influence of breast cancer risk factors and intramammary biotransformation on estrogen homeostasis in the human breast

Understanding intramammary estrogen homeostasis constitutes the basis of understanding the role of lifestyle factors in breast cancer etiology. Thus, the aim of the present study was to identify variables influencing levels of the estrogens present in normal breast glandular and adipose tissues (GLT and ADT, i.e., 17β-estradiol, estrone, estrone-3-sulfate, and 2-methoxy-estrone) by multiple linear regression models. Explanatory variables (exVARs) considered were (a) levels of metabolic precursors as well as levels of transcripts encoding proteins involved in estrogen (biotrans)formation, (b) data on breast cancer risk factors (i.e., body mass index, BMI, intake of estrogen-active drugs, and smoking) collected by questionnaire, and (c) tissue characteristics (i.e., mass percentage of oil, oil%, and lobule type of the GLT). Levels of estrogens in GLT and ADT were influenced by both extramammary production (menopausal status, intake of estrogen-active drugs, and BMI) thus showing that variables known to affect levels of circulating estrogens influence estrogen levels in breast tissues as well for the first time. Moreover, intratissue (biotrans)formation (by aromatase, hydroxysteroid-17beta-dehydrogenase 2, and beta-glucuronidase) influenced intratissue estrogen levels, as well. Distinct differences were observed between the exVARs exhibiting significant influence on (a) levels of specific estrogens and (b) the same dependent variables in GLT and ADT. Since oil% and lobule type of GLT influenced levels of some estrogens, these variables may be included in tissue characterization to prevent sample bias. In conclusion, evidence for the intracrine activity of the human breast supports biotransformation-based strategies for breast cancer prevention. The susceptibility of estrogen homeostasis to systemic and tissue-specific modulation renders both beneficial and adverse effects of further variables associated with lifestyle and the environment possible.

Exploring Association of Breast Pain, Pregnancy, and Body Mass Index with Breast Tissue Elasticity in Healthy Women: Glandular and Fat Differences.

Breast sonoelastography is a relatively novel ultrasound (US) method that enables estimation of tissue stiffness to estimate the elasticity of normal breast tissue and seek to correlate it with well-known breast cancer risk factors. Two hundred women of different age were included in the study and completed a questionnaire about personal, familiar, and reproductive history. Glandular and fatty tissue elasticity in all breast quadrants was measured by shear wave elastography (SWE). Mean elastographic values of breast tissue were calculated and compared to personal history risk factors. Elasticity of normal glandular tissue (66.4 kilopascals (kPa)) was higher than fatty tissue (26.1 kPa) in all breast quadrants and in both breasts. Lower outer quadrant (LOQ) had the lowest elasticity values of both parenchyma and fat. Higher elasticity values of breast tissue were confirmed in the left breast than in the right breast. Glandular and fat tissue elasticity negatively correlated with body mass index (BMI). Women with mastodynia had higher glandular elastographic values compared to subjects without breast pain. Nuliparity was also associated with higher elasticity of glandular breast tissue. The results of this study are promising and could, over time, contribute to a better understanding of glandular breast tissue elasticity as a potential risk factor for breast cancer.

An evaluation and ranking of evolutionary algorithms in segmenting abnormal masses in digital mammograms

Breast cancer is the most common cancer in women worldwide and the second main cause of cancer mortality after lung cancer. Up to now, there still no prevention nor early symptoms of breast cancer. Early detection can decrease significantly the mortality rate as the disease can be treated at an early stage. X-Ray is the current screening method that helps in detecting the most two common abnormalities of the breast, masses and micro-calcifications. However, interpreting mammograms is challenging in dense breasts as the abnormal masses and the normal glandular tissue of the breast have similar characteristics. Recently, the evolutionary algorithms have been widely used in image segmentation. In this paper, we evaluate and compare the performance of six most used evolutionary algorithms, invasive weed optimization (IWO), genetic algorithm (GA), particle swarm optimization (PSO), electromagnetism-like optimization (EMO), ant colony optimization (ACO), and artificial bee colony (ABC) in terms of clustering abnormal masses in the breast, particularly dense and extremely dense breasts. This evaluation is conducted based on quantitative metrics including Cohen’s Kappa, correlation, and false positive and false negative rates. The evolutionary algorithms are then ranked based on two multi-criteria decision analysis methods, the Preference Ranking Organization Method for the Enrichment of Evaluations (PROMETHEE) and the Graphical Analysis for Interactive Aid (GAIA).

Ultrasonographic review of pediatric breast masses among Nigerian children in a tertiary hospital.

Background:Breast masses occur infrequently in children and adolescents. Most of these masses have proved that benign and conservative approach is the management of choice. Consequently, imaging has become crucial. The knowledge of the ultrasonographic features of childhood and adolescent breast masses is needed for age appropriate medical care.Aim:The aim of this study was to describe and document the ultrasonographic spectrum of breast masses in children and adolescents (0–19) years seen in the Ahmadu Bello University teaching hospital, Zaria.Materials and Methods:A 2-year retrospective review of breast sonograms of 25 consecutively presenting children and adolescents (3 males and 22 females) who had palpable breast masses. Ultrasound scans were performed with a Mindray Machine DC-8 using the linear transducer at 7.5–12 MHz transducer frequency. Histopathological confirmation of the solid masses was also obtained. The statistical analysis of the data collected was done using the SPSS software version 20 (SPSS Inc., Chicago, IL, USA).Results:The patients were between 40 days and 19 years old (mean 14.8 years and standard deviation 4.1). The ultrasonographic findings were those of infections, benign tumoral lesions and pubertal endocrine changes. Overall, fibroadenoma was the most common mass, seen in 14 (56%) of the patients. Other findings were simple cysts, non-puerperal and puerperal mastitis, juvenile papillomatosis and normal glandular pubertal breast tissue. The three male patients had gynaecomstia, pseudogynaecomastia and cystic lymphangioma of the chest wall presenting as unilateral breast masses, respectively. There was no malignancy recorded in any of the patients.Conclusion:Ultrasonographically, benign masses predominate which is concordant with surgical findings. Familiarity with these features would obviate the need for unnecessary invasive procedures which should be reserved for only deserving cases.

Abstract 4926: Loss of deiodinase type 3 expression distinguishes patients with poor prognosis in breast cancer

Abstract Background: Breast cancer is a highly heterogeneous disease and the identification of biomarkers that predict tumor biological behavior is warranted in improving patient survival. Thyroid hormones (THs) are critical regulators of cellular processes, and TH status alterations are known to contribute to cancer progression through all the hallmarks of cancer. Clinical studies associate THs levels with breast cancer mortality, and THs have been shown to influence breast cancer proliferation, apoptosis, and migration in in vitro models. Type 3 deiodinase (DIO3) is the main enzyme responsible for TH inactivation and disturbed DIO3 expression has been demonstrated in several human neoplasias. Here, we aimed to evaluate expression patterns and the prognostic significance of DIO3 in breast cancer. Methods: The expression of DIO3 was assessed by immunohistochemistry in a primary cohort of 53 samples of breast tissue and was validated in a second cohort using the RNA-Seq data from TCGA database (BRCA study). We assessed DIO3 expression in both populations according to retrieved clinicopathological information. For methylation analysis, DNA methylation data from the TCGA-BRCA study were obtained. Regulation of DIO3 gene was investigated in MCF-7 and MDA-MB-231 cell lines. Results: DIO3 expression was present in normal and tumoral breast glandular tissue. DIO3 mRNA expression was found to be reduced in tumor samples when compared to normal tissue (p&amp;lt;0.0001). Unexpectedly, loss of DIO3 expression was associated with increased mortality (HR 4.29; 95% CI 1.24-14.7) in the primary cohort. We then validated this finding in the secondary cohort. Patients with low DIO3 expression exhibited reduced overall survival (OS) when compared to those higher levels of DIO3 expression. Five-year OS rates were 90.4% and 77.4% in the high and low expression groups, respectively (p=0.0002). Among patients with metastasis, five-year OS rate was 70% in the high DIO3 group and 0% in the low DIO3 group (p=0.038). Additional experiments were performed to determine DIO3 regulation in breast cancer. In MCF-7 and MDA-MD-231 cells, DIO3 was subject to T3 stimulation and was under the regulation of MAPK pathway, as MAPK inhibition resulted in a 50% reduction of DIO3 expression (p=0.004). Methylation analysis revealed that DIO3 gene promoter is hypermethylated in tumoral cells when compared to normal tissue (p &amp;lt;0.0001). Conclusions: DIO3 is expressed in normal and tumoral breast tissue. Here, we demonstrate a role for DIO3 as a prognostic marker in breast cancer, as loss of DIO3 expression distinguishes breast cancer patients with poor overall survival. Moreover, our fındings suggest the utility of DIO3 expression for stratifıcation of patients with metastasis. The finding that DIO3 gene is regulated by the MAPK pathway and that gene promoter is hypermethylated in breast cancer might have therapeutic implications. Citation Format: Iuri M. Goemann, Vicente R. Marczyk, Mariana Recamonde-Mendoza, Marcia S. Graudenz, Simone M. Wajner, Ana Luiza Maia. Loss of deiodinase type 3 expression distinguishes patients with poor prognosis in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4926.

Low-Dose Perfusion Computed Tomography for Breast Cancer to Quantify Tumor Vascularity: Correlation With Prognostic Biomarkers.

The aim of this study was to investigate the feasibility of using low-dose perfusion computed tomography (CT) in breast cancers for quantification of tumor vascularity and to correlate perfusion indexes with prognostic biomarkers. This preliminary study was approved by our institutional review board. Signed informed consent was obtained from all 70 enrolled patients with invasive breast cancers. Low-dose perfusion CT was performed with the patient in the prone position using a spectral CT device set at 80 kVp and 30 mAs (1.30-1.40 mSv). Images were analyzed using commercial software applying the maximum slope algorithm. On CT perfusion maps, perfusion (mL/min per 100 mL), blood volume (mL/100 g), time-to-peak enhancement (second), and peak enhancement intensity (HU) were measured in the tumor, normal breast glandular tissues, and fat. Tumor grade, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67 level were evaluated using histopathology. Statistically, CT perfusion indexes of the tumor and normal glandular tissues or fat were compared using the Wilcoxon signed-rank test, and CT indexes were correlated with histological characteristics using the Mann-Whitney U or Kruskal-Wallis tests. We also correlated CT indexes with magnetic resonance imaging enhancement characteristics. In breast cancers, perfusion, blood volume, and peak enhancement intensity values were significantly higher, and time to peak was shorter than in normal glandular tissues and fat (P < 0.001). Perfusion increased significantly in high-grade, ER-, or HER2+ cancers (P < 0.05). Time to peak decreased in ER-, HER2+, and high-grade cancers or in those with high Ki67 levels (P < 0.05). Peak enhancement intensity significantly increased in high-grade cancers (P < 0.05). HER2 overexpressing cancers showed significantly higher perfusion and shorter time to peak than luminal-type cancers (P < 0.05). Perfusion increased and time to peak decreased significantly in cancers with washout enhancement patterns on magnetic resonance imaging. Low-dose perfusion CT in the prone position is feasible to quantify tumor vascularity in breast cancers, and CT perfusion indexes are significantly correlated with prognostic biomarkers and molecular subtypes of breast cancer.

Measurement of breast-tissue x-ray attenuation by spectral imaging: fresh and fixed normal and malignant tissue

Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. In mammography, measurement of breast density, dose estimation, and differentiation between cysts and solid tumours are example applications requiring accurate data on tissue attenuation. Published attenuation data are, however, sparse and cover a relatively wide range. To supplement available data we have previously measured the attenuation of cyst fluid and solid lesions using photon-counting spectral mammography. The present study aims to measure the attenuation of normal adipose and glandular tissue, and to measure the effect of formalin fixation, a major uncertainty in published data. A total of 27 tumour specimens, seven fibro-glandular tissue specimens, and 15 adipose tissue specimens were included. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, from which x-ray attenuation as a function of energy can be derived. The spread in attenuation between samples was relatively large, partly because of natural variation. The variation of malignant and glandular tissue was similar, whereas that of adipose tissue was lower. Formalin fixation slightly altered the attenuation of malignant and glandular tissue, whereas the attenuation of adipose tissue was not significantly affected. The difference in attenuation between fresh tumour tissue and cyst fluid was smaller than has previously been measured for fixed tissue, but the difference was still significant and discrimination of these two tissue types is still possible. The difference between glandular and malignant tissue was close-to significant; it is reasonable to expect a significant difference with a larger set of samples. We believe that our studies have contributed to lower the overall uncertainty of breast tissue attenuation in the literature due to the relatively large sample sets, the novel measurement method, and by clarifying the difference between fresh and fixed tissue.

Abstract A36: Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to terminal duct lobular unit involution in Caucasian and African American women: The Susan G. Komen Tissue Bank

Abstract Background: Insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 play important roles in carcinogenesis, particularly for breast cancer. However, little is known about whether the IGF system influences histologic characteristics of normal glandular tissue and whether relationships vary by race. Lesser degrees of age-related terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. We examined the associations of IGF measures with TDLU involution of normal breast using standardized TDLU measures. Methods: Among 715 Caucasian and 283 African American (AA) women with normal breast tissue samples from the Komen Tissue Bank, serum concentrations of IGF-I and IGFBP-3 were quantified using enzyme-linked immunosorbent assay (ELISA). Hematoxilyn and eosin-stained tissue sections were assessed for numbers of TDLUs (“TDLU count”) and acini/TDLU. Zero-inflated Poisson regression models with a robust variance estimator were used to estimate associations of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 molar ratio (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. We also tested for interactions by race using likelihood ratio tests. Results: AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p=0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p&amp;lt;0.0001); the differences persisted after adjustment for additional covariates including BMI and parity/age at first birth. Postmenopausal IGFBP-3 was inversely associated with TDLU count among both AA (RR T3vs.T1=0.49, 95% CI=0.28-0.84, p-trend=0.04) and Caucasian (RR T3vs.T1=0.63, 95% CI=0.41-0.99, p-trend=0.04) women. In premenopausal women, higher IGF-I:IGFBP-3 ratios were associated with higher TDLU count in Caucasians (OR T3vs.T1=1.33, 95% CI=1.01-1.31, p-trend=0.04) but not in AA (OR T3vs.T1=0.65, 95% CI=0.42-1.00, p-trend=0.05) women. There was no statistically significant interaction by race (p-interaction≥0.10). Conclusions: Our data suggest the potential role of the IGF system, particularly IGFBP-3, in TDLU involution of the normal breast among both Caucasian and AA women. Citation Format: Hannah OH, Ruth M. Pfeiffer, Roni T. Falk, Hisani N. Horne, Jackie Xiang, Michael Pollak, Louise A. Brinton, Anna Maria V. Storniolo, Mark E. Sherman, Gretchen L. Gierach, Jonine D. Figueroa. Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to terminal duct lobular unit involution in Caucasian and African American women: The Susan G. Komen Tissue Bank [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A36.

High expression of ALDOA and DDX5 are associated with poor prognosis in human colorectal cancer.

PurposeThe identification of prognostic markers for colorectal cancer (CRC) is needed for clinical practice. Fructose-bisphosphate aldolase A (ALDOA) and DEAD box p68 RNA helicase (DDX5) are commonly overexpressed in cancer and correlate with tumorigenesis. However, association between expression of ALDOA and DDX5, and CRC outcome has not been reported.Patients and methodsWe used 141 formalin-fixed paraffin-embedded (FFPE) specimens collected from 105 patients with CRC treated at the Affiliated Hospital of Guilin Medical University and the People’s Hospital of Liuzhou. We performed tissue microarray based immunohistochemistry to explore expression features and prognostic value (overall survival, OS; disease-free survival, [DFS]) of ALDOA and DDX5 in CRC tissues. The prognostic values were evaluated using Kaplan–Meier analysis, and Cox regression analyses.ResultsALDOA and DDX5 were highly expressed in CRC tissues and liver metastatic CRC tissues compared with normal glandular epithelium tissues (all p<0.05). Interestingly, primary CRC tissues highly expressing ALDOA or DDX5 had poor outcome (p<0.0001 for both OS and DFS for ALDOA; p=0.001 for OS; and p=0.011 for DFS for DDX5) compared with patients who had low expression of those proteins. Furthermore, multivariate Cox analysis showed that ALDOA/DDX5 combination was an independent risk factor for OS and ALDOA was an independent risk factor for DFS.ConclusionHigh levels of ALDOA and DDX5 contribute to the aggressiveness and poor prognosis of CRC. ALDOA/DDX5 expression could be a biomarkers for the prognosis of CRC.

UDP-sugar accumulation drives hyaluronan synthesis in breast cancer

Increased uptake of glucose, a general hallmark of malignant tumors, leads to an accumulation of intermediate metabolites of glycolysis. We investigated whether the high supply of these intermediates promotes their flow into UDP-sugars, and consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human breast cancer biopsies, the levels of enzymes contributing to their synthesis, and their association with the hyaluronan accumulation in the tumor. The content of UDP-GlcUA was 4 times, and that of UDP-GlcNAc 12 times higher in the tumors as compared to normal glandular tissue obtained from breast reductions. The surge of UDP-GlcNAc correlated with an elevated mRNA expression of glutamine-fructose-6-phosphate aminotransferase 2 (GFAT2), one of the key enzymes in the biosynthesis of UDP-GlcNAc, and the expression of GFAT1 was also elevated. The contents of both UDP-sugars strongly correlated with tumor hyaluronan levels. Interestingly, hyaluronan content did not correlate with the mRNA levels of the hyaluronan synthases (HAS1–3), thus emphasizing the role of the UDP-sugar substrates of these enzymes. The UDP-sugars showed a trend to higher levels in ductal vs. lobular cancer subtypes. The results reveal for the first time a dramatic increase of UDP-sugars in breast cancer, and suggest that their high supply drives the accumulation of hyaluronan, a known promoter of breast cancer and other malignancies. In general, the study shows how the disturbed glucose metabolism typical for malignant tumors can influence cancer microenvironment through UDP-sugars and hyaluronan.

Role of Bcl-2 and Bax in parotid gland atrophy.

To investigate the expression and correlation of B-cell lymphoma-2 (Bcl-2) and Bax in the parotid gland after leading duct ligation in rat. Atrophy of the right parotid was induced by ligating the right Stensen's duct of rats. Immunohistochemical labeling was performed to study the changes in number and distribution of Bcl-2 and Bax in each step of glandular atrophy, and every group at 1, 3, 5, 7, 14, 21, 30, 60, 90, 150, 180 days after ligation. Bcl-2 and Bax showed a low level of expression in normal glandular tissues. At different time points after the ligation of the main duct, Bcl-2 was highly expressed in the duct cells, and the absorbance value reached a peak value at 21-day (3.02+0.10). The 1 D expression of Bax was found in some of the cells in the 3 D, and the expression of Bax reached the peak (1.99+0.10), and the expression of Bcl-2 and Bax were decreased in some cells. Bcl-2/Bax ratio increased at 1 day-21 day, and then decreased and stabilized. The expression of Bax and Bcl-2 after ligation of the parotid gland is closely related to the process of the parotid gland atrophy.