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.

Activation of oncogenic signaling kinase PAK1 by ionising radiation confers an aggressive phenotype in head and neck squamous cell carcinoma.

Head and neck squamous cancers are very aggressive tumors often diagnosed in late stages with poor prognosis. HNSCCs are usually treated by a course of radiation (IR) therapy and followed by surgery. These treatment regimens fail to bring a complete response. Molecular signatures in tumors are attributed to this response and an improved understanding of the signaling events could offer new avenues for therapy. Here, we show that P21 activated kinase-1 (PAK1) - an oncogenic signaling serine/threonine kinase, is activated upon exposure to IR and this leads to an accelerated tumorigenic character in HNSCC cells. Our results show that PAK1 is highly expressed in HNSCC cell lines, as compared to normal buccal mucosa cells and when HNSCC cells were exposed to IR, they show activated PAK1 and an aggressive phenotype as determined by in vitro functional assays. PAK1 levels were elevated in HNSCC as compared to adjacent normal oral tissues and our results also show convincing evidence of activated PAK1 in patient tumor samples of post- IR treatment as compared to pre-IR treatment and is associated with poor survival. Pak1 Knockout (KO) clones in HNSCC cells showed that they were more sensitive to IR as compared to wild type (wt) cells. This altered sensitivity to IR was attributed to enhanced DNA damage response modulated by PAK1 in cells. Overall, our results suggest that PAK1 expression in HNSCC could be a critical determinant in IR therapy response and silencing PAK1 is likely to be a treatment modality to improve clinical outcomes.

Incidental ancient schwannoma of the posterior mediastinum in a young male: a rare scenario.

Ancient schwannoma is a distinctive type of schwannoma occurring mostly in the retroperitoneum. The presentation in the posterior mediastinum is rare. The term 'ancient' represents a group of neurogenic tumours showing degenerative changes with marked nuclear atypia. A 26-year-old man was incidentally detected to have an upper mediastinal mass lesion in the chest X-ray. MRI chest revealed a mixed signal intensity lesion in the left side upper para spinal region of the posterior mediastinum. The patient underwent left posterior thoracotomy and excision of the mass was done. Postoperative period was uneventful. The histopathological feature was typical of Ancient schwannoma. The patient is on regular follow-up and disease free until.

Double Pathology: Malignant Epithelial Ovarian Tumor and Germ Cell Tumor (Choriocarcinoma), a Rare Coexistence.

Surface epithelial stromal tumors account for approximately 60% of all ovarian tumors and approximately 90% of all ovarian malignancies. Sex cord stromal tumors account for 7% of all malignant ovarian tumors. Germ cell tumors make up only 3-7% of malignant ovarian tumors. A combination of serous carcinoma of the ovary and choriocarcinoma is rare. Until today such combination has been documented only in six cases in the English literature. Here, we describe a case of ovarian serous carcinoma, where histopathology revealed a combination of serous carcinoma with adjacent choriocarcinoma component in the extraovarian peritoneal deposits. A 64-year-old post-menopausal female was diagnosed to have stage IV ovarian cancer. She received six cycles chemotherapy. Subsequently she underwent optimal cytoreductive surgery. Microscopically, monomorphic histology (serous carcinoma) was noted in both the ovaries and dimorphic histologies (serous carcinoma and choriocarcinoma) in the sigmoid mesocolon nodule, omentum and left subdiaphragmatic nodules. Metronomic chemotherapy continued and patient is on regular follow-up for the past 1 year with stable disease. Recognition of choriocarcinomatous components in ovarian carcinomas is important because of its association with aggressive behavior. In spite of the aggressive histology, the patient is surviving for the past 1 year. Different chemotherapeutic regimens have been used in cases of mixed choriocarcinoma and carcinoma, but established chemotherapeutic regimens have not been described. Chemotherapeutic regimens that target both components have been advocated and used. The absence of choriocarcinoma in ovarian primary and its presence in the extraovarian peritoneal deposits have not been described in the English literature so far. This case is being presented for its rarity.

Deep soft-tissue leiomyoma of the forearm mimicking a primary bone tumor of the ulna.

Leiomyomas of the soft tissues are rare in general, and extremely uncommon in the forearm. In general, leiomyomas are benign soft-tissue tumors that occur where smooth muscles are present. We present a case of soft-tissue leiomyoma of the forearm eroding the midshaft of the ulna, with emphasis on radiological diagnosis and histopathological correlation.