TAP1-TAP2 heterodimeric complexes are recognized as the transporter associated with antigen processing of major histocompatibility complex class I peptides for recognition by tumor-specific cytotoxic ...T lymphocytes. In this study, we investigated the immunohistochemical expression of TAP1 and TAP2 in 160 patients with breast cancer and correlated their expression levels with clinicopathologic parameters. The median age of the patient cohort was 52.5 years (range, 30-86 years). Both TAP1 and TAP2 immunohistochemical expression levels correlated significantly with breast cancer characteristics (P < .001). TAP1 expression levels were low to negative in stage I breast tumors. TAP1 and TAP2 levels were significantly higher in grade 3 tumors than low-grade (grade 1 and 2) tumors. TAP1 and TAP2 expression levels were not significantly different among different levels of HER2-expressing tumors and did not vary by estrogen and progesterone receptor status or patient age. Both TAP1 and TAP2 overexpression in breast cancer might be an indicator of an aggressive breast tumor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby ...patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.
Gastrointestinal neuroectodermal tumors (GNETs) are malignant tumors frequently arising within the muscularis propria of the gastrointestinal tract and often extend into the submucosa and subserosa. ...The stomach is the second most common site of incidence of GNETs after the small intestine. The most important differential of GNET is the clear cell sarcoma-gastrointestinal (CCS-GI). Both share similar morphological as well as molecular features and show S100 positivity; however, the lack of melanocytic differentiation in GNET distinguishes it from CCS-GI. Both typically show rearrangements of the EWSR1 gene, with t(12;22) (q13;q12) EWSR1-ATF1 or t(2;22) (q34;q12) EWSR1-CREB1 fusions. We present a case of a 71-year-old man with an incidentally discovered GNET in the gastric cardia and fundus.
Breast cancer is the most common cancer in a woman with a five-year survival of patients with metastatic disease is estimated at 23%. Ado-trastuzumab emtansine (T-DM1) is a HER2-antibody drug ...conjugate currently approved for the treatment of HER2-positive pre-treated metastatic breast cancer (BC). We report a case of recurrent metastatic breast cancer with unusually lengthy progression-free survival (PFS) on T-DM1 chemotherapy. She was diagnosed with Triple Positive Stage IIIC multifocal invasive ductal carcinoma of the left breast. After completing neoadjuvant chemotherapy, she underwent a bilateral mastectomy. Final pathology showed partial response. Postoperatively, she received adjuvant chemotherapy and radiation therapy. She was started on Q21 days trastuzumab following completion of adjuvant chemotherapy. Systemic imaging showed liver lesions and biopsy confirmed recurrence. She was started on T-DM1, endocrine therapy with anastrozole was continued. She is currently status post 45 cycles. T-DM1 was approved for the treatment (single-agent) of HER2-positive, metastatic BC based on phase III data from the EMILIA and TH3RESA study. Median PFS in the T-DM1 arm was 9.6 months. Herein, we present a case of a woman with recurrent triple positive metastatic BC with a lengthy progression-free survival on T-DM1 chemotherapy.
Triple negative breast cancer (TNBC) comprises 15-20% of all invasive breast cancer and is associated with a poor prognosis. As therapy options are limited for this subtype, there is a significant ...need to identify new targeted approaches for TNBC patient management. The expression of the folate receptor alpha (FRα) is significantly increased in patients with TNBC and is therefore a potential biomarker and therapeutic target. We optimized and validated a FRα immunohistochemistry method, specific to TNBC, to measure FRα expression in a centrally confirmed cohort of 384 patients with TNBC in order to determine if expression of the protein is associated with invasive disease-free survival (IDFS) and overall survival (OS). The FRα IHC demonstrated exceptional performance characteristics with low intra- and interassay variability as well as minimal lot-to-lot variation. FRα expression, which varied widely from sample to sample, was detected in 274 (71%) of the TNBC lesions. In a multivariable model adjusted for baseline characteristics, FRα expression was associated with improved IDFS (HR = 0.63,
= 0.01) but not with OS. The results demonstrate the potential of targeting the FRα in the majority of TNBC patients and suggest that variable expression may point to a need to stratify on FRα expression in clinical studies.
Objective:
We aimed to compare the safety and efficacy of pectoral nerve block (Pecs) I and II with control or other techniques used during breast cancer surgeries such as local anesthesia, ...paravertebral block, and erector spinae plane block (ESPB).
Methods:
We searched 4 search engines (PubMed, Cochrane Library, Scopus, and Web of Science) for relevant trials, then extracted the data and combined them under random-effect model using Review Manager Software.
Results:
We found 47 studies, 37 of them were included in our meta-analysis. Regarding intraoperative opioid consumption, compared with control, a significant reduction was detected in Pecs II (standardized mean difference SMD=−1.75, 95% confidence interval CI −2.66, −0.85,
P
=0.0001) and Pecs I combined with serratus plane block (SMD=−0.90, 95% CI −1.37, −0.44,
P
=0.0002). Postoperative opioid consumption was significantly lowered in Pecs II (SMD=−2.28, 95% CI −3.10, −1.46,
P
<0.00001) compared with control and Pecs II compared with ESPB (SMD=−1.75, 95% CI −2.53, −0.98,
P
<0.00001). Furthermore, addition of dexmedetomidine to Pecs II significantly reduced postoperative opioid consumption compared with Pecs II alone (SMD=−1.33, 95% CI −2.28, −0.38,
P
=0.006).
Conclusion:
Pecs block is a safe and effective analgesic procedure during breast cancer surgeries. It shows lower intra and postoperative opioid consumption than ESPB, and reduces pain compared with control, paravertebral block, and local anesthesia, with better effect when combined with dexmedetomidine.
Sarcoidosis is a multisystem, inflammatory granulomatous disease that rarely involves breast tissue. The pathophysiology of this chronic granulomatous condition is not well understood but is thought ...to be multifactorial, involving environmental influences causing an amplified immune response. A key histomorphology feature in sarcoidosis is the presence of non-necrotizing granulomas. In this case, we report a 41-year-old African-American man with a known history of sarcoidosis of the lung who presented with gynecomastia and bilateral breast tenderness with palpable nodules. Subsequent biopsy and microscopic examination of the breast nodules revealed diffuse involvement with non-necrotizing granulomas in both breasts. A final diagnosis of extensive sarcoidosis involving breast tissue was rendered after excluding other causes of non-necrotizing granulomas. The patient underwent a bilateral mastectomy to remove the breast nodules. This case discusses sarcoidosis involving an unusual site.
Granular cell tumors (GCTs) are rare neoplasms of neuroectodermal origin characterized by large polygonal cells with abundant eosinophilic and granular cytoplasm. GCTs rarely affect the lungs, with ...only a few cases reported in the literature. The pathophysiology of this Schwann cell-derived condition is not well understood but is thought to be due to recurring genetic mutations. GCTs have been linked with Noonan syndrome. Here, we report the case of a 17-year-old caucasian male who presented with partial upper airway obstruction due to a GCT. This case promotes awareness among pathologists and clinicians for this condition in the workup of patients presenting with upper airway obstruction.
Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer. It is commonly associated with deficient mismatch repair proteins and has a strong association with ...Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here, we discuss an interesting case of MC of the colon that was metastatic on presentation and constituted a diagnostic challenge.
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