Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure.

Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor-2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN-LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.

Exploring the Relationship Between CD 166 Expression and Breast Imaging Reporting and Data System (BI-RADS) Scores in Breast Cancer Patients and Healthy Volunteers.

BACKGROUND: This research embarked on a crucial endeavor to clarify the connection between levels of CD166 expression and the established Breast Imaging Reporting and Data System (BI-RADS) grading system. Through a comprehensive exploration of this correlation, the objective was to ascertain if CD166 could function as an additional biomarker, enhancing the predictive effectiveness of the BI-RADS classification. METHOD: This prospective observational study involved 81 women with histopathologically confirmed early breast tumors and 81 radiologically confirmed healthy breast volunteers. The BI-RADS scores of all the participants included in the study were recorded. Before starting treatment, serum, saliva, and urine samples were collected. The CD166 levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: The study involved the analysis and comparison of the mean and standard deviations of CD166 expression in serum, saliva, and urine across various BI-RADS categories. Notably, statistically significant differentiation was found (p=0.00) across all samples spanning the spectrum of BI-RADS categories. CONCLUSION: A progressive rise in CD166 concentration coincides with the increasing gradient of the BI-RADS category, implying a possible link between CD166 and breast cancer progression and severity.

Comparison of p63 immunohistochemistry and shear wave elastography in the diagnosis of indeterminate breast lesions: A prospective study.

Purpose: To evaluate the accuracy of breast shear wave elastography (SWE) and p63 immunohistochemistry (IHC) in the diagnosis of indeterminate breast lesions. Methods: Based on detailed clinical examination and a combination of X-ray mammography/B-mode ultrasound with SWE, a total of 40 patients with breast lumps (BI-RADS 4) were included. Patients with previous diagnosis of breast cancer and a previous history of surgery, chemotherapy, or radiotherapy in the same breast as the present lesion were excluded. Core needle biopsy of the breast lesion was performed, and p63 IHC staining was performed. A final histopathological report of the definitive procedure was considered as the gold standard. The sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy were calculated for each modality. Results: The mean age of the patients included in the study was 50.85 ± 13.53 years. Of the 40 patients recruited, 23 were clinically malignant and 17 were benign. The sensitivity, specificity, PPV, NPV, and accuracy of SWE were 91.3%, 94.1%, 95.5%, 88.9%, and 92.5% and those of p63 IHC were 95.7%, 100%, 100%, 94.4%, and 97.5%, respectively. Overall, the parametric values were higher for p63 IHC as compared to clinical examination and elastography. The area under the ROC curve (AUC) for p63 IHC (.978) was higher than those for SWE (.927) and clinical examination (.898). Conclusion: SWE and p63 IHC are highly reliable novel modalities that demonstrate enhanced diagnostic accuracy of indeterminate breast lesions aiding in the early initiation of appropriate treatment and reducing the number of women subjected to biopsy or short-term follow-up for benign-appearing solid breast lesions.

Imaging and pathological discordance amongst the plethora of breast lesions in breast biopsies.

INTRODUCTION: Imaging-guided breast tissue biopsy has become an acceptable alternative to open surgical biopsy for nonpalpable breast lesions. Discussion of abnormal results of the correlation between imaging and pathological findings can be very challenging as it can assist in decision-making with regard to the further treatment options by arriving at a comprehensive diagnosis. MATERIALS AND METHODS: This was a retrospective study. Radiological data from imaging-guided breast biopsies of 500 patients during a 6-year period was collected and classified by a specialist radiologist as per the BI-RADS format. Histopathology reports were studied and discordance analyzed. RESULTS: A total of 500 cases were reviewed. Approximately 33% (168) cases fell into the BI-RADS 3 category, 24.4% (122) into the BI-RADS 4, and 37% (187) into BI-RADS 5 categories. Approximately 50% (n = 250) cases were benign, 2.6% (13) belonged to the high-risk category, and 47.4% (237) were malignant. The number of discordant cases was 12 (2.4%), mostly due to technical factors. Sensitivity of biopsies to detect malignancy was 85%, specificity was 96%, and accuracy of biopsy in diagnosing cancer was 90%. DISCUSSION: The "triple assessment" is the most sensitive method for detecting early breast cancer. An effective communication pathway must be established between a clinician, radiologist, and pathologist for surgical excision in discordance as it carries a high prevalence of carcinoma in these lesions. CONCLUSION: In discordant cases, either due to abnormal results of imaging or of abnormal pathological findings, the final decision is based on two concordant findings, out of the three parameters. This involves a multidisciplinary breast conference and an active participation by the pathologist.

The Significance of Topoisomerase II Alpha in Invasive Breast Carcinoma.

Background Topoisomerase II alpha (Top 2 A) protein has been shown to be a proliferation marker associated with tumour grade. The current study evaluated the prognostic impact of Top 2 A protein on luminal breast cancer and its utility as an independent prognostic marker. Immunohistochemical expression of Top 2 A in breast cancer and its correlation with the tumour type, size, lymph node metastases, grade and ER/PR positivity. Methodology Ethics committee approval was taken and 65 cases of Invasive breast carcinoma presenting to the Department of Pathology at a tertiary care centre in South India were studied. Patient details including age, tumour type, tumour size, tumour grading, estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2/neu) status and pathologic stage was studied. Immunohistochemistry (IHC) work-up for Top 2 A expression was done and evaluated. Results Of the 65 histological sections of breast cancers, 29/65 showed nuclear positivity for Top 2 A. Node positive tumours 17/65 stained positive for Top 2 A. Stage I tumours 2/65, stage II tumours 12/65 and stage III 14/65 stained positive for Top 2 A. Among the HER2/neu-positive tumours, 22/65 stained for Top 2 A and among ER/PR-positive 9/65 cases were positive for Top 2 A. Triple-negative tumours 5/65 stained for Top 2 A. Conclusion Higher Top 2 A expression was seen in higher stage tumours. HER2/neu-positive tumours significantly showed a correlation with Top 2 A positivity. Therefore, Top 2 A expression can be considered an individual prognostic factor in breast carcinoma.

Molecular dysregulations underlying the pathogenesis of endometriosis.

Endometriosis is a crippling disease characterized by the presence of endometrium-like tissue or scar outside the uterine cavity, commonly confined to the peritoneal and serosal surfaces of the pelvic organs. 10-15% of women in reproductive age are estimated to be affected by endometriosis. Most of these patients present with infertility and suffer from pelvic pain. The benign disease rarely progresses to malignancy. Regardless of its high prevalence, the pathogenesis of the disease is not fully understood. Treatment options for endometriosis are limited and are often based on a symptomatic approach. The unavailability of proper diagnostic approaches, fewer therapeutic options, and sparse understanding of molecular alterations are responsible for the continued disease burden. Exploring the molecular elements causing the pathogenesis of endometriosis may lead to a number of breakthroughs in the treatment of the illness, such as the discovery of new biomarkers for diagnosis and therapeutic targets that can be a guide to better prognosis and reduced recurrence. The goal of this review is to provide the reader a critical understanding of the disease by summarizing the genetic, immunological, hormonal, and epigenetic deregulations that support the molecular basis for development of endometriotic cyst, with a special focus on the study models needed to analyze these changes in the endometriotic microenvironment.

Wired for Surgical Success: Our Experience with Preoperative Ultrasound-Guided Wire Localization of Impalpable Breast Lesions.

Aims The purpose of this study was to review our experience with preoperative ultrasound-guided wire localization and to identify our rate of successful localization and subsequent excision. Materials and Methods At our institution, we performed preoperative wire localization for 28 impalpable breast lesions in 27 women (1 patient underwent wire localization for bilateral breast lesions), between April 2016 and August 2019. We used a Toshiba APLIO2 ultrasound machine and a linear probe (7-12 MHz) to visualize lesions and needle-wire systems comprising a 20-gauge needle with preloaded wire to localize lesions. We analyzed the percentage of specimen mammograms with wire in situ and percentage of excised specimens showing margins free of tumor, along with imaging features, BI-RADS (Breast Imaging-Reporting and Data System) categories, and histopathological and molecular diagnosis of the lesions. Results All specimen mammograms confirmed the presence of wire in situ, except one (96.4%); in the latter case, postponement of surgery due to intractable cough was suspected to have caused wire displacement. All malignant specimens showed margins free of tumor (100%). Conclusions Our results show that wire localization is extremely effective in providing crucial preoperative insight into the precise location of an impalpable lesion. Despite the advent of nonwire localization devices such as radioactive seeds, radar reflectors, magnetic seed markers, and radiofrequency identification tags, wire localization remains the most widely practiced method, especially in resource-limited settings. Its high degree of accuracy serves as a key factor in the successful outcome of breast conservation surgery for impalpable breast lesions.

MR-guided focused ultrasound surgery: A novel non-invasive technique in the treatment of adenomyosis -18 month's follow-up of 12 cases.

BACKGROUND: Adenomyosis is a gynecological condition of the uterus, characterized by the presence of ectopic endometrial tissue in the myometrium. Hysterectomy, uterine artery embolization, and endometrial ablation therapy are the various surgical treatment options available for adenomyosis. A novel and globally upcoming technique is MR-guided focused ultrasound surgery "MRgFUS," which is a promising non-invasive surgical treatment option. This study was carried out to determine the effectiveness of MRgFUS in the symptomatic management of adenomyosis. SUBJECTS AND METHODS: This study was carried out as a long-term follow-up study among 12 cases of adenomyosis, which were treated by MR-guided focused ultrasound. In all these participant's, three parameters - symptom severity score (SSS), menstrual pain score accessed using visual analogue score (VAS), and number of approximate pads used during menstruation were recorded prior to the treatment and on follow-up at 3, 9, and 18 months, respectively. The Friedman's test was used to test the difference in the values of scores before and after treatment. RESULTS: There was a significant improvement in the SSS, VAS, and the numbers of sanitary napkins used after surgery and sustained during the long-term follow-up. These values were statistically significant (P < 0.05). CONCLUSION: MRgFUS can be used in successful treatment of adenomyosis/focal adenomyoma by careful selection of the participant, good planning, and proper monitoring of the technique during ablation.

Bilateral mammary Paget disease in a young adult female.

Mammary Paget disease is an uncommon malignancy of the breast that presents with ulceration or eczema of the nipple and is almost always associated with an underlying breast carcinoma. This disease is most commonly seen in the fifth and sixth decades of life and is almost always unilateral. The diagnosis of mammary Paget disease is generally based on clinical findings, confirmed by histopathologic examination. Mammographic and ultrasonographic findings may be nonspecific for malignancy, with 50% of cases showing negative findings. Magnetic resonance imaging can be used as a diagnostic tool to detect clinically occult cancer with nonspecific findings on mammogram and ultrasonogram. In this article, we are presenting a rare case of a young woman with biopsy-proven bilateral mammary Paget disease, for which bilateral modified radical mastectomy was done, followed by adjuvant chemotherapy and radiotherapy.

Efficacy of Dipeptide-Coated Magnetic Nanoparticles in Lung Cancer Models Under Pulsed Electromagnetic Field.

Lung cancer is the leading cause of cancer deaths and the overall 5-year survival rate is less than 17%. Hyperthermia is an alternative approach for the treatment of lung cancer and is associated with fewer side effects. We employed ironoxide nanoparticles in inducing localized hyperthermia in lung cancer cells using a pulsed electromagnetic field (PEMF). We synthesized, characterized and determined the uptake of dipeptide-coated iron oxide nanoparticles. Further, their ability in inducing localized hyperthermia in PEMF on lung cancer cells was assessed. Results showed nanoparticles are non-cytotoxic and showed enhanced cellular uptake in lung cancer cells. In vivo studies in nude mice lung tumor xenografts confirmed the presence in the tumors. Lung cancer cells pretreated with dipeptide-coated magnetic nanoparticles upon PEMF exposure induced cell death.

Back to Basics - 'Must Know' Classical Signs in Thoracic Radiology.

There are a few signs in radiology which are based on many common objects or patterns that we come across in our routine lives. The objective behind the association between such common objects and the corresponding pathologies is to make the reader understand and remember the disease process. These signs do not necessarily indicate a particular disease, but are usually suggestive of a group of similar pathologies which will facilitate in the narrowing down of the differential diagnosis. These signs can be seen in different imaging modalities like plain radiograph and computed tomography. In this essay, we describe 24 classical radiological signs used in chest imaging, which would be extremely helpful in routine clinical practice not only for radiologists but also for chest physicians and cardiothoracic surgeons.

Internal hernias: surgeons dilemma-unravelled by imaging.

Internal hernias may present as intestinal obstruction and account for 0.5 to 4.1 % of all cases. Clinical diagnosis of internal hernias is often difficult and thus imaging studies plays an important role in the early diagnosis. It is vital for the radiologist to be familiar with the various types of internal hernias and their radiological features so that prompt diagnosis and early intervention can be made.

Atypical presentation of gastrointestinal stromal tumours-a case report.

Gastrointestinal stromal tumors (GISTs) are benign mesenchymal tumors of the gastrointestinal tract (GIT). Their clinical presentations are variable. We report a case of a 31-year-old man who presented with pain in the abdomen and vomiting. CT abdomen revealed a large exophytic mass in the epigastrium with enhancement pattern similar to hemangioma. No relationship of the mass could be made out with the adjacent structures on CT, histopathology proved it to be a GIST.

Diagnostic accuracy of 64-slice multidetector computed tomography in evaluation of post-coronary artery bypass grafts in correlation with invasive coronary angiography.

64-slice multidetector computed tomography (MDCT) allows more reliable and non-invasive evaluation of the coronary artery bypass grafts for occlusion or stenosis both in symptomatic and asymptomatic patients and also progression of disease in native coronary vessels.

Pictorial essay: Anatomical variations of paranasal sinuses on multidetector computed tomography-How does it help FESS surgeons?

With the advent of multidetector computed tomography (MDCT), imaging of paranasal sinuses prior to functional endoscopic sinus surgery (FESS) has become mandatory. Multiplanar imaging, particularly coronal reformations, offers precise information regarding the anatomy of the sinuses and its variations, which is an essential requisite before surgery.

Hydatid cyst: Anywhere, everywhere.

Hydatid cyst is a parasitic infection that primarily affects the liver but which can be found anywhere in the body. This case involves spontaneous dissemination of hydatid cyst disease, a rare occurrence in the absence of any intervention or trauma.

Fused supernumerary kidney.

A partially fused supernumerary kidney with bifid ureters was diagnosed in a 35-year-old female patient using ultrasound and triple-phased computed tomography (CT). The CT also revealed two separate renal arteries supplying each of the left kidney and multiple left renal veins, forming a common trunk to drain into the inferior vena cava. Supernumerary kidney is a rare congenital anomaly; fewer than 100 cases have been reported over the years. A fused supernumerary kidney is rarer still.

Case report: Perinephric lymphangiomatosis.

Perirenal lymphangiomatosis is a rare benign malformation of the lymphatic system. We report here a case of bilateral perirenal and parapelvic involvement with a normal excretory collecting system.

Ultrasound versus MRI in the diagnosis of fetal head and trunk anomalies.

OBJECTIVE: To compare antenatal sonography and magnetic resonance (MR) imaging (MRI) in the diagnosis of fetal head and trunk anomalies. METHODS: Forty pregnant women with fetal anomalies on ultrasound (US) examination underwent MRI. The MR examination was done by a radiologist who was provided with the US data. The MR images were then read by one of the two radiologists who were blinded to the US data. They were however told that the region of interest was (1) head-neck or (2) trunk or (3) both. Antenatal US and MRI findings were compared with postnatal diagnosis. Postnatal evaluation included plain radiograph, US, computed tomography, MRI, surgery, physical evaluation and autopsy. RESULTS: Sixty anomalies were detected in the 40 women studied. This included 36 central nervous system (CNS), 7 thoracic, 7 gastrointestinal, 8 genitourinary and 2 face-neck anomalies. In the evaluation of CNS and thoracic anomalies, more number of confident diagnoses could be obtained by MRI when compared with that by US. In the detection of gastrointestinal and genitourinary anomalies, there was no significant difference between the two modalities. CONCLUSION: More number of confident diagnoses could be obtained by MRI when compared with that by US, in the evaluation of fetal CNS and thoracic anomalies. MRI can be used in complex fetal anomalies as a supplementary tool following US.