The statuses of HER2 expression and mismatch repair in endometrial clear cell carcinoma.

High-grade endometrial carcinomas (HGEC) are difficult to classify. With the current use of HER2-based therapy in serous carcinoma, a diagnosis of clear cell carcinoma (CCC) has the potential to exclude patients from receiving therapy. Therefore, we examined HER2 expression in our CCC patients. The preparations of 8 patients with CCC who underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection were re-evaluated. Patients did not have any prior treatment. Histopathologic parameters that were evaluated include cytoplasmic clearing, nuclear atypia, mitotic activity, hobnail architecture, hyalinized cores, hyaline globules, stratification of epithelial lining papillae, or glandular structures, and highly atypical cell layers. Immunohistochemically, HER2, ER, PR, HNF1ß, Napsin A, MLH1, MSH2, MSH6 and PMS2 were applied. HER2 staining pattern, ASCO/CAP protocol used for endometrial carcinom was used. HER2 was positive in 3 of our 8 CCC patients (37.5%). While all of our HER2 + cases were Napsin A and HNF1ß positive, MMR proteins were intact and ER and PR were negative. Two patients had wild type p53 and 1 patient had aberrant p53 staining. Considering that there is not always a consensus between SC and CCC, even among gynecopathologists, tumor heterogeneity and different tumor components may exist, and while patients may be diagnosed with CCC and benefit from HER2 therapy, there is also a possibility that they may not benefit from the treatment. The fact that 37.5% of our CCC cases were HER2 + is a finding with strong implications for the therapeutic approach. As a result of our study, in patients with CCC, if MMR is intact and ER-PR is negative, regardless of the p53 staining pattern, HER2 testing may be an objective screening method for patients who are likely to benefit from HER-targeted therapy. Consequently, patients with a diagnosis of CCC can be candidates for future clinical trials of HER2-targeted therapy.

A BRIEF SYNOPSIS OF MONOCLONAL ANTIBODY FOR THE TREATMENT OF VARIOUS GROUPS OF DISEASES.

Monoclonal antibodies (mAbs) are increasingly being prescribed to patients and investigated in the field of medicine and research. This class of medication is unique due to its ability to be engineered into targeting a specific receptor. Numerous studies and reviews have reported the efficacy, potency, and clinical usage of mAbs in the treatment of a variety of diseases ranging from autoimmune disorders to malignant cancers. However, very few publications classify and provide a brief synopsis of mAbs that includes their pharmacological profiles. mechanisms of action, uses, and side effects in a concise manner. Therefore, this review aims to classify the current mAbs drugs used in clinical practice according to system diseases by providing a brief summary for each of them. For example, regarding cardiovascular disorders, mAbs such as Abciximab, Bevacizumab, and Digoxin Immune Fab will be reviewed. Denosumab, used to treat musculoskeletal disorders, will be also discussed. In addition, mAbs such as Adalimumab, Eculizumab, Natalizumab used in autoimmune disorders and Alemtuzumab, Trastuzumab, Cetuximab, and Rituximab that are prescribed for tumors will be reviewed. Finally, we shall discuss two mAbs that are IL-6 antagonists, Tocilizumab and Siltuximab, which are in ongoing clinical trials as potential treatments of COVID-19. The mAbs have profound benefits against chronic and malignant conditions, and the overall purpose of this review is to illustrate the basic pharmacological profiles of mAbs that physicians may find useful in establishing their management protocols.

Transtuzumab induced organizing pneumonia: a case report.

BACKGROUND: Patients with metastatic breast cancer often have pulmonary symptoms with varying aetiologies. Transtuzumab is an extremely important drug used in the treatment of Her 2 neu over-expressing breast cancers. In this report we describe a case of organizing pneumonia associated with use of transtuzumab in metastatic breast cancer. Only three such cases have previously been reported. CASE DESCRIPTION: A 43 year old lady with Her 2 neu 3+, estrogen and progesterone receptor positive, metastatic breast cancer was started on weekly transtuzumab and albumen bound paclitaxel. She was admitted with an episode of bilateral pneumonitis after her fourth dose of therapy. It was managed conservatively with antibiotics. Subsequently, single agent transtuzumab was administered resulting in an anaphylactoid reaction followed by worsening dyspnoea requiring hospitalization and oxygen support for 3 days. DISCUSSION AND EVALUATION: The pneumonitis warranted further investigations including bronchoscopy which were performed. Bronchoscopic biopsy was consistent with a diagnosis of organizing pneumonia. Transtuzumab was stopped and she was started on steroids (dexamethasone). She improved remarkably and was discharged home on hormonal therapy, lapatinib and tapering doses of steroids. CONCLUSION: Organizing pneumonia closely mimics infection or progressive disease and can be difficult to diagnose in the setting of malignancy. Correct diagnosis is of paramount importance since delay in treatment can result in significantly adverse patient outcomes.

Antibody drug conjugates.

Antibody drug conjugates (ADCs) have emerged as a viable option in targeted delivery of highly potent cytotoxic drugs in treatment of solid tumors. At the time of writing, only two ADCs have received regulatory approval with >40 others in clinical development. The first generation ADCs suffered from a lack of specificity in amino acid site-conjugations, yielding statistically heterogeneous stoichiometric ratios of drug molecules per antibody molecule. For the second generation ADCs, however, site-specific amino acid conjugation using enzymatic ligation, introduction of unnatural amino acids, and site-specific protein engineering hold promise to alleviate some of the current technical limitations. The rapid progress in technology platforms and antibody engineering has introduced novel linkers, site-specific conjugation chemistry, and new payload candidates that could possibly be exploited in the context of ADCs. A search using the Clinical Trial Database registry ( www.clinicaltrials.gov ), using the keyword 'antibody drug conjugate', yielded ~270 hits. The main focus of this article is to present a brief overview of the recent developments and current challenges related to ADC development.