Expression of Human epidermal growth factor receptor 2, Survivin, Enhancer of zeste homolog -2, Cyclooxygenase-2, p53 and p16 molecular markers in Gall bladder carcinoma.

INTRODUCTION: Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging. MATERIALS AND METHODS: This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry. RESULTS: Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 - 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ2 = 9.886, P = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ2 = 7.017, P = 0.037 and χ2 = 5.861, P = 0.033) respectively. CONCLUSIONS: The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.

Expression and clinicopathological correlation of Ki-67 in gallbladder carcinoma.

INTRODUCTION: Gallbladder cancer is an aggressive cancer with short median survival from the time of diagnosis. Improved understanding of the pathological molecular mechanisms of gallbladder carcinogenesis is important to refine the diagnosis, prognosis, and also to develop novel targeted therapies for patients with advanced Gallbladder cancer (GBC) malignancy. Ki-67 is a marker of cell proliferation and its detection by immunohistochemistry is considered to be an effective method for the detection of prognosis in several tumors. In the present study, we have analyzed expression of immunohistochemical marker Ki-67 in gallbladder carcinoma and its correlation with clinicopathological and radiological parameters. MATERIALS AND METHODS: This prospective observational study was conducted from December 2017 to July 2020. The patients of newly diagnosed gallbladder cancer were enrolled as per the inclusion and exclusion criteria defined in the study protocol. Contrast-enhanced computer tomography of the chest and abdomen and serum tumor markers such as carbohydrate antigen (CA)-19.9, carcinoembryonic antigen, and CA 125 were done. Immunohistochemical expression of Ki-67 was evaluated on biopsy tissue from the gallbladder mass. RESULTS: Fifty newly diagnosed patients of carcinoma gallbladder were included in the present study. The correlation was studied between clinicodemographic parameters and Ki-67, but no association was found with age, gender, and symptoms. There was a weak positive correlation between Ki-67 and direct bilirubin, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase (P = 0.094; 0.126; 0.542; and 0.328, respectively). There was a weak positive correlation between body mass index (Kg/m2) and Ki-67, but this correlation was not statistically significant (P = 0.304). CONCLUSIONS: Ki-67 is a marker of proliferation and it correlated with histological differentiation, jaundice and liver function tests, presence of stones, and location of metastases but did not correlate with stage and extent of disease.

Molecular characterization of lung carcinomas: A study on diagnostic, predictive, and prognostic markers using immunohistochemical analysis at a Tertiary Care Center in Uttarakhand, India.

INTRODUCTION: Focused studies in different geographic regions would delineate the underlying biological differences and molecular alterations in non-small cell lung cancer (NSCLC) worldwide. Previous studies in literature have documented limited characterization by studying a minimal number of biological markers. This study was done to evaluate expression of multiple immunomarkers including diagnostic, prognostic, and predictive markers in NSCLC for its characterization. MATERIALS AND METHODS: This was an observational study conducted on 60 consecutive cases of NSCLC. Immunomarkers comprising of p63, p40, TTF-1, napsin A, B-Raf, c-Met, phospho-AKT (P-AKT), PTEN, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR) and K-Ras, synaptophysin, chromogranin and pan-cytokeratin were evaluated on paraffin-embedded tissue sections of NSCLC. RESULTS: Age of patients with NSCLC in our study ranged from 35 to 90 years, and 93.3% of them were chronic smokers. 93.3% of cases presented in late stages (Stages III and IV) and 78% of cases were squamous cell carcinoma (SCC). EGFR positivity was noted in 83.3% of cases. ALK was positive in one case while C-Met and PTEN immunopositivity was noted in only two cases. Ten cases showed positivity for K-Ras and 90% of these were SCC. Ten cases were positive for B-Raf and 80% of these were SCC. 30% of cases showed immunopositivity for P-AKT. None of the molecular markers was found to have statistically significant correlation with clinicopathological parameters. CONCLUSION: SCC is the predominant histological subtype of NSCLC in the region of Uttarakhand, India, with a high proportion of cases harboring EGFR mutation. Variable expression of K-Ras, P-AKT, ALK 1, and PTEN in NSCLC signifies that molecular profile of every case is individualistic and independent. We attribute this to ethnicity, influence of implicated substance or metabolite in tobacco, and variable mutations incurred in tumor cells over a period of time.

Embracing the change: Resuming advanced trauma training in the COVID-19 era.

BACKGROUND: Trauma is slowly regaining its pre-COVID-19 status in terms of prevalence. Advanced trauma training cannot be deferred indefinitely in the current pandemic owing to defense requirements and disaster preparedness in vulnerable regions. Advanced Trauma Life Support (ATLS) India resumed ATLS and Advanced Trauma Care For Nurses (ATCN) courses at one civilian and one military site. METHODS: Stakeholders of respective centers for advanced trauma training deliberated over safe means to resume ATLS and ATCN. Meticulous screening of all participants and pre- and post-course tracking were deemed the most important components for the safe resumption of courses. 'Paperless' course, 'open-air' skill stations, 'payment protection', 'buddy system', point of care sanitizer installation, packed food, and potable beverages were major organizational changes. Participants above 60 years and with uncontrolled comorbidities were not enrolled. RESULTS: Two ATCN, one ATLS (civilian), and one combined ATLS-ATCN (military) were conducted. 78 delegates trained by 32 faculties and 13 personnel. All underwent daily thermal scanning and smartphone application-based COVID-19 tracking. Manikins were utilized instead of moulages and instructors took up the role of nursing assistants in Initial Assessment. Exit exams were conducted with full PPE precautions at the military site and mask-distancing precautions at the civilian site. High fidelity simulator was used at one station at the civilian site. Expenses at the civilian site per course were USD 570 lower than conventional courses. There was no incidence of COVID-19 in any of the 123 participants at 14 days follow up. CONCLUSION: With stringent participant selection and moderate precautions, ATLS and ATCN can be resumed safely in the current COVID-19 pandemic. To the best of our knowledge and after a thorough search of published English literature, this is the first paper reporting on resuming Advanced trauma training in the COVID-19 era.

Advanced Trauma Care for Nurses (ATCN): A Single-Center Analysis of Trauma Nurses Knowledge Gaps.

BACKGROUND: Trauma is a global cause of death and disability, and trauma systems are not well developed in low- and middle-income countries. Training of nurses in trauma care is of utmost importance to improve the organization and delivery of trauma care. OBJECTIVE: This study aimed to identify common knowledge gaps and develop study aids to improve nurses' performance taking the Advanced Trauma Care for Nurses (ATCN) course. METHODS: This is a descriptive, single-center study of the multiple-choice final examinations of the ATCN course conducted over 1 year in the All India Institute of Medical Sciences, Rishikesh, Level I trauma center. The questions missed by candidates were compiled, and the wrong options were tabulated. The most commonly missed questions were identified, and the most commonly marked wrong option was analyzed vis-a-vis the correct answer. Each error was classified into either a theoretical error or a practice-based error. RESULTS: Ninety-six nurses attended 6 courses from June 2019 to June 2020. Of the theoretical-based questions, the top 3 categories of most missed questions were geriatric trauma (n = 13; 81.2%), massive transfusion (n = 35; 72.9%), and traumatic brain injury (n = 35; 72.9%). Of the practice-based questions, the top 3 categories of most missed questions were dislocated extremity management (n = 54; 79.4%), basic airway (n = 31; 64.5%), and shock management (n = 30; 62.5%). CONCLUSIONS: Periodic identification and categorization of the ATCN course examination's most frequent knowledge gaps allow instructors to develop teaching aids to enhance instructor teaching and improve trauma nurses' knowledge.

Clinicopathological significance of immunohistochemical expression of Filamin A in breast cancer.

BACKGROUND: Filamin A is an actin-crosslinking protein expressed in many malignancies, although its prognostic and therapeutic role in breast cancer is not studied. There is enigma regarding its dual role in cancer, the tumor-progressing or tumor-suppressing effects depending on the site to which it localizes in the cell. The current study aimed to detect Filamin A expression in breast cancer and its association with other biomarkers and other clinicopathological parameters and established risk factors in breast cancer so that it can be a potential site for targeted therapy. MATERIALS AND METHODS: One hundred female patients of histologically proven breast cancer who presented to our hospital over a 2-year period were included in the study. None of the patients received prior radiotherapy, chemotherapy, or immunotherapy. Patients with recurrent breast cancer are not included in the study. All study cases are subjected to immunohistochemistry for estrogen receptor, progesterone receptor, Her2 neu, and ki-67 from core biopsy tissue of cases diagnosed as breast carcinoma. Tissue sections were subjected to immunohistochemistry with anti-Filamin A. RESULTS: Filamin A is expressed in 69% of cases of invasive breast cancer in our study. There was no statistically significant relationship of Filamin A immunoexpression with histological grade, age, parity, oral contraceptive use, smokeless tobacco use, TNM staging, clinical staging, clinical prognostic staging, and also ER, PR, Her2 neu, and ki-67 status (P > 0.05). Thus, it appears to be an independent biomarker in breast carcinoma. Filamin A was expressed only in the cytoplasm in all our study cases. Filamin A expression can be observed in adjacent normal breast tissue and benign fibroadenoma tissues also, but the pattern of expression is mainly membranous with cytoplasmic positivity. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. CONCLUSION: No significant correlation could be found between Filamin A expression and clinicopathological parameters in our study. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. Filamin A immunoexpression should be further correlated with metastasis-free survival period of breast cancer patients.

Identification of suitable reference genes in blood samples of carcinoma lung patients using quantitative real-time polymerase chain reaction.

INTRODUCTION: Lung cancer (LC), among all other cancers, is the leading cause of death worldwide, while the third most common cancer-causing mortality in India. Several techniques of the assay for early detection of cancer that improve survival rates have been employed in tissues and cell lines. Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) is one of the most common techniques employed for gene expression studies for the normalization of a target gene using a reference gene (RG). The present study used the three most common RGs: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ß-Actin, and 18s ribosomal ribonucleic acid (18s rRNA), which were assessed by qPCR to validate, as of which is a more effective RG in blood samples of LC patients. MATERIALS AND METHODS: A total of thirty participants with LC of non-small cell and small cell type were included along with twenty healthy controls. Ribonucleic acid (RNA) isolated from peripheral blood mononuclear cells was quantified, prepared for complementary deoxyribose nucleic acid synthesis, and analyzed for expression of three RG on RTqPCR. RESULTS: Expression levels as Ct values of studied RG were reported as mean ± standard deviation for GAPDH (26.97 ± 5.107), ß-actin (20.5 ± 2.3), and 18s rRNA (25.10 ± 4.075). GAPDH showed the lowest expression, whereas ß-actin showed the highest expression among the studied RG in subjects of LC. The expression of GAPDH and 18s rRNA were statistically significantly lower than ß-actin (p < 0.0001), whereas expression levels of GAPDH and 18s rRNA were comparable. However, the expression level of only ß-actin in LC patients was comparable with healthy controls with P < 0.1611 at 95% confidence interval. CONCLUSION: It is concluded that ß -actin may be considered the most suitable RG isolated and studied from peripheral blood mononuclear cells using RT qPCR in LC.

Intrathoracic Ewing's sarcoma in an adult masquerading as lung abscess.

Intrathoracic extraskeletal Ewing's sarcoma (EES) is a relatively uncommon malignant tumour. Here, we present a scenario involving an adult man in his 20s with a large intrathoracic EES that manifested as a lung abscess. Preoperative diagnostic tests were inconclusive; hence, the patient underwent an exploratory thoracotomy for the excision of the mass. Histopathology revealed a small round blue cell tumour, and immunohistochemistry, along with fluorescence in situ hybridisation, confirmed the diagnosis of Ewing's sarcoma. Adjuvant chemoradiotherapy was recommended, but the patient did not comply. A year later, he presented with a recurrence of the intrathoracic mass and subsequently received adjuvant chemotherapy. Currently, he is in remission.

Primary Sjogren's syndrome presenting as hypokalaemic periodic paralysis and acute pancreatitis.

Renal tubular acidosis is a well-known consequence of primary Sjogren's syndrome (pSS), but a rare manifestation similar to acute pancreatitis in pSS. Here, we discuss the case of a woman in her 50s, who presented to a tertiary care hospital with recurrent episodes of sudden-onset weakness in all four limbs, recurrent vomiting and epigastric pain. She had non-anion gap metabolic acidosis with hypokalaemia and was diagnosed with pSS with hypokalaemic periodic paralysis. She was also diagnosed with acute pancreatitis based on elevated amylase and lipase levels and CT findings. The article highlights the diverse spectrum of clinical manifestations of pSS, including renal and pancreatic involvements, which can be rare consequences of the disease.

High-Fidelity, Indigenously Prepared, Low-Cost Moulage as a Valid Simulation Tool to Improve Trauma Education.

Background Simulation-based trauma education facilitates repeated practice in a controlled and safer environment for the learner without any risk to the patient's well-being. Moulage contributes to the perception of reality during training using standardized patients. However, the high cost of commercial moulage items is often prohibitive for regular use. This study aimed to assess the effectiveness of indigenously prepared, low-cost moulage as a valid simulation tool to improve trauma education, explore possible replacements of commercial moulage products, and determine their merits and demerits. Methodology Readily available economic items were used to make low-cost moulage on the simulated patients to replicate trauma victims. A cross-sectional design used a pre-validated Modified Moulage Authenticity Rating Scale to collect data from 61 participants of Advanced Trauma Life Support and Advanced Trauma Care for Nurses courses to analyze the effectiveness and fidelity of moulage. Results In total, 54 (89%) participants scored the low-cost moulage to provide high fidelity effectively. The majority of respondents graded the authenticity of moulage as good. Overall, 46 (75%) participants felt moulage injuries were quite realistic. All agreed that the moulage-based simulation offered a good teaching-learning alternative to assess and manage trauma victims. Further, 45 (73%) participants felt they were in an actual clinical situation, and 58 (95%) stated it could help them in their clinical practice. Conclusions Indigenously prepared, low-cost moulage is a feasible and cost-effective means to enhance fidelity in simulation-based trauma education. It can also be a possible replacement for commercial moulage. Further research is needed to rigorously evaluate the effectiveness of indigenously prepared, cost-effective moulage in trauma education to enhance patient care outcomes. This technique can also be easily translated into other simulation-based medical education domains.

Comparison of Sexual Function after Thermal Ablation Versus Loop Electrosurgical Excision Procedure (LEEP) for Cervical Intraepithelial Neoplasia (CIN 2 and 3): A Randomized Controlled Trial.

BACKGROUND: The prevention of cervical cancer can be achieved by treating high-grade cervical precancerous lesions. Treatment options for cervical precancer include excisional procedures, and ablation treatments. Despite the long pre-invasive course of the disease, literature addressing sexual function post-treatment for cervical pre-invasive lesions is scarce. This study aims to bridge this gap and assess the sexual function and the acceptability, efficacy, safety, and complications of loop electrosurgical excision procedure (LEEP) versus thermal ablation. METHODS: The prospective open-label randomized controlled trial recruited women aged 22-55 with histologically confirmed Cervical Intraepithelial Neoplasia (CIN) 2 and 3 lesions. Participants were randomly allocated to either thermal ablation or LEEP. All cases were followed up with a Pap smear at three- and six-months post treatment. Sexual health assessments were conducted using a questionnaire at baseline and 3 months post-procedure. Secondary outcome measures included comparison of acceptability, pain, and side effects between the two treatment measures. RESULTS: Out of 1356 screened cases, 60 were included in the study and randomized in two groups. The groups had similar baseline characteristics. Duration of LEEP was longer than thermal ablation (25.33 vs. 20.67 minutes), with higher pain reported 10 minutes post-procedure in the LEEP group. Three months post-procedure, both groups showed comparable acceptability and symptom relief. Sexual function parameters significantly improved in the thermal ablation group compared to LEEP, including satisfaction, desire, lubrication, flexibility, and ability to reach climax. CONCLUSION: LEEP and thermal ablation are effective treatments for CIN with similar efficacy at 6 months. Thermal ablation demonstrated advantages in procedure time and post-procedural pain but exhibited varying effects on sexual function, improving satisfaction and desire. In contrast, LEEP showed a decrease in satisfaction and potential alterations in lubrication and flexibility. Larger-sample, longer-term studies are recommended for further insights.

Expression of Survivin, CK7, ASH1, HMGB3, L587S, and CLCA2 in Peripheral Blood of Lung Cancer Patients by Real-Time Polymerase Chain Reaction.

Introduction The objective of the present study was to identify gene expression in peripheral blood by a real-time polymerase chain reaction (PCR) technique in patients who have lung carcinoma. Material and methods Peripheral blood samples of patients with non-small cell and small cell lung cancer were collected. Target genes included survivin, CK7, ASH1, HMGB3, L587S, and CLCA2. ß-Actin was the reference gene. If the mean CT (threshold cycle) value for a target gene is ≥40, the gene expression is considered undetectable. Results Fifty patients with lung carcinoma were included and 30 healthy controls. Out of the six genes, survivin showed 26.8 times fold change as compared to controls; ASH1 and L587S were 0.54 and 0.06, respectively; and HMGB3, CLCA2, and CK7 had non-significant fold change in comparison to controls. The overall detection rate of the six target genes examined in lung cancer was 84%, with 42 out of 50 patients testing positive. Higher stages and ASH1 (p = 0.031), CK7 (p = <0.001), and HMGB3, p = 0.011 were associated significantly. CLCA2 had higher expression in patients without adrenal metastases (p = 0.044). Conclusions Lifestyle and geographical variation might be a probable cause of variable gene expression as compared to other studies. However, further research is needed to determine the clinical implication of these markers, especially in larger groups of early-stage patients.

Lymph node evaluation and nodal metastasis prediction in epithelial ovarian cancers: A retrospective study.

Objective: To identify consensus regarding lymph node (LN) evaluation in epithelial ovarian cancer (EOC). The objective of the present study was to evaluate surgico-pathological findings, LN involvement, and the prediction of LN metastasis via preoperative imaging and intraoperative assessment in women with EOC. Materials and Methods: Women with EOC who underwent cytoreductive surgery (CRS) between Jan 2019 to June 2022 were included. The distribution of histology, stage, and LN metastasis was studied. The predictive value of serum cancer antigen (CA)-125, instead of and radiologically and surgically enlarged LNs with final LN histopathology was studied. Results: A total of 96 women with EOCs underwent CRS. Fifty women (52%) underwent primary CRS and 46 women (48%) underwent interval CRS. Seventy-five women (78.13%) with EOC underwent pelvic and/or para-aortic lymphadenectomy, out of which 23 (30.67%) were histologically positive. High-grade serous carcinoma was the commonest (n=55, 73.33%) histology. The majority of women, 56 (74.67%) were stage III or IV at presentation. Complete cytoreduction was achieved in 59 (78.66%) patients. The receiver operating characteristics curve showed a cutoff for CA-125 of 1360 U/mL (area under the curve 0.702, p=0.002) for LN metastases. Both radiologically and surgically enlarged LNs significantly predicted LN metastasis on histopathology (p=0.02 and 0.006 respectively). The combined sensitivity, specificity, positive predictive value and negative predictive value of both contrast enhanced computed tomography (CECT) and surgically enlarged LNs were 78.26%, 57.69%, 45%, and 85.71%, respectively. Conclusion: Serous histology, high-grade tumors, highCA-125 levels, and suspicious LNs on CECT or during surgery were significantly associated with LN metastasis. However, considering the false-negative rate of 21.74%, the combination of radiologically and surgically enlarged LNs cannot be used as the sole surrogate marker for lymphadenectomy.

Systematic Review and Meta-Analysis of the Diagnostic Accuracy of the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy in Diagnosing Breast Cancer.

OBJECTIVES: The primary objective is to determine the accuracy of fine-needle aspiration biopsy (FNAB) in breast lesions reported according to the International Academy of Cytology (IAC) Yokohama system for reporting breast FNAB. The participants include any patient presenting with any breast lesion found suitable for FNAB. The target condition was breast cancer. The secondary objective was to study the proportion of inadequate FNAB in the selected studies. METHODS: PubMed/MEDLINE and Embase were searched for studies having all the following key search terms: Breast AND FNAB AND Diagnostic Accuracy published in the time frame of 2017 to May 16, 2022. The Cochrane and PROSPERO databases, citations of selected articles and articles citing the selected articles were also searched. Studies assessing the diagnostic accuracy of breast FNAB in diagnosing breast cancer, which had at least 75 subjects (and at least 20 subjects each in the benign and malignant FNAB groups), were selected. The reference standard was histopathology (or adequate clinical follow-up for benign disease). Studies were screened independently by two researchers, with a consensus reached among the authors in cases of conflict. The risk of bias and applicability were assessed using the QUADAS-2 tool. Sensitivity and specificity at each diagnostic cut-off were assessed by bivariate generalized linear mixed-model meta-analysis. The area under the receiver operating characteristics curve (AUC) and inadequacy rate were assessed by random-effects meta-analysis. The confidence intervals of sensitivity, specificity, and AUC were examined against a value of 0.95. RESULTS: Twenty-two studies, all of which were cross-sectional single-gate studies, were selected with a total of 10,886 subjects with a primary breast lesion having concurrent FNAB and reference standard reports. Sensitivity and specificity, with 95% confidence intervals, were 0.978 [0.968, 0.985] and 0.832 [0.76, 0.886] for the diagnostic cut-off of "Atypical considered positive for malignancy," 0.916 [0.892, 0.935] and 0.983 [0.97, 0.99] for the cut-off of "Suspicious of Malignancy considered positive," and 0.763 [0.706, 0.812] and 0.999 [0.994, 1] for the cut-off of "Malignant considered positive." The overall AUC was 0.975 [0.962, 0.984]. FNAB sampling without imaging guidance was associated with lower inadequacy. DISCUSSION: There is strong evidence that the overall accuracy, sensitivity for "Atypical category considered positive" and specificity when "Suspicious or Malignant categories are considered positive" of FNAB are high when using the categories of the IAC Yokohama Reporting System, demonstrating the usefulness of FNAB in diagnosing breast cancer.

Detecting Human Epidermal Growth Factor Receptor 2 (HER2) Amplification: Proof of Concept of an Alternative Approach.

BACKGROUND: There are multiple genes that are co-amplified along with human epidermal growth factor receptor 2 (HER2) in chromosome 17. GRB7 and PGAP3 are two such genes. We hypothesize that the protein products of these genes may serve as immunohistochemistry (IHC) markers for detecting HER2 amplification in breast cancer. METHODS: Tissue sections from one hundred and thirty-five primary breast carcinoma cases were subjected to immunohistochemical staining for antibodies against HER2, GRB7, and PGAP3 and graded on a scale of 1 to 3. Both membranous staining and cytoplasmic staining were assessed for GRB7 and PGAP3. For equivocal HER2 IHC positivity, fluorescent in situ hybridization was performed to get the final HER2 status. RESULTS: IHC staining for GRB7 and PGAP 3 was a moderate to strong predictor for HER2 status (area under the curve (AUC) of 0.768, 0.868,0.754, and 0.790 for GRB7 membranous staining, GRB7 cytoplasmic staining, PGAP3 membranous staining, and PGAP3 cytoplasmic staining respectively). A combination of GRB7 cytoplasmic and PGAP3 membranous staining resulted in an AUC of 0.905 (95% CI 0.855-0.954), while a combination of GRB7 and PGAP3 cytoplasmic staining resulted in an AUC of 0.902 (95% CI 0.851-0.953). CONCLUSION: The point estimates for the AUC of GRB7 and combined GRB7 and PGAP3 in predicting the AUC suggest a strong predictive ability of these markers to predict HER2. With further refinement in technique, cytoplasmic staining and membranous IHC staining for GRB7 and PGAP3 have potential to serve as surrogate markers for HER2 status. The strategy of using protein products of co-amplified genes of HER2 is likely to be successful in technical validation.

Is "Initial Size of the Graft the Real Culprit behind Primary Contraction of Full-Thickness Skin Graft"? - A Cross-Sectional Study.

Background Primary contraction of full-thickness graft has been traditionally quoted to be 40%. There are lacunae in literature to elaborate on the factors influencing it ever since. Methods About 75 subjects who underwent full-thickness grafting procedures to resurface small defects were included in the study. The initial and final graft dimensions after primary contraction were traced on X-ray templates and the percentage of contraction was evaluated using the graphical method. This was further correlated with age, collagen, elastic matrix metalloproteinases-1 (MMP-1) and -2 content along with dermal thickness of the skin specimen sent from the graft. Results The primary contraction of the graft had a very significant correlation only with the initial size of graft harvested with a linear regression of 33.3% and a Spearman's correlation of 0.587 significant at a p -value of 0.001. Conclusion This study though preliminary tries to highlight an important factor that primary contraction of grafts is a physical phenomenon independent of its contents like collagen, elastin, or MMP-1 and -2 or age and dependent on its initial size of harvest instead.