High-grade Carcinoma Research Articles

7928 A "PTH-Mediated" Hypercalcemia Of Malignancy

Abstract Disclosure: N. Sekhon: None. R.J. Bingham: None. Background: We present a challenging diagnostic case of a 73-year-old female with PTH-mediated hypercalcemia in the presence of new metastatic uterine cancer. Case: A 73-year-old female with a past medical history of hypertension and abdominal aortic aneurysm was seen in the hospital for hypercalcemia. She endorsed constipation, fatigue, and generalized weakness for the past few weeks. This was the second hospitalization related to hypercalcemia over the period of 10 days. During the previous hospitalization, her admission calcium was 17 mg/dL and was treated with IV fluids, calcitonin, and zoledronic acid. There was a history of intentional weight loss of about 30-40 lbs in the last 3 months by reducing carbohydrate intake. The patient had a 40-pack years of smoking history. There was no family history of calcium disorders or cancers. Home medications included amlodipine 10 mg QD, docusate sodium 100 mg BID, senna 1 tab QHS, and Vit D 5000 U QD. On physical examination, she was hemodynamically stable but appeared confused and lethargic. The rest of the examination was unremarkable. Laboratory results were remarkable for hypercalcemia (Ca: 13.3 mg/dL), hypophosphatemia (Phosphorus: 2.3 mg/dL), and elevated PTH of 418.3 pg/mL (Ref. Range: 18.4-80.1 pg/mL). CT abdomen/ pelvis revealed innumerable ill-defined hypodense lesions throughout the liver concerning metastatic disease and a 5 cm mass in the uterine fundus. The patient was worked up with the view of hypercalcemia related to malignancy. However, PTHrP (PTH-related peptide) came back normal, which was checked twice during both hospitalizations. Liver biopsy showed metastatic high-grade carcinoma highly suspicious for GYN malignancy with negative PTH staining. Imaging studies for localization including CT soft tissue neck and CT 4D parathyroid with and without contrast failed to show any parathyroid lesions. Endometrial biopsy obtained during subsequent hospitalization showed high-grade adenocarcinoma with focal squamous differentiation. Immunohistochemical staining identified scattered positivity for PTH. The patient was managed as per hypercalcemia of malignancy guidelines with IV fluids and denosumab. Discussion: Hypercalcemia of malignancy due to ectopic PTH secretion has been reported in < 1% of cases. Only two endometrial cancer cases with ectopic PTH have been reported in the literature. PTH-mediated hypercalcemia is seen in primary hyperparathyroidism, parathyroid cancers, or ectopic PTH. In all cases of hypercalcemia of malignancy, primary hyperparathyroidism should be ruled out in the presence of elevated PTH. Diagnosing ectopic PTH secretion by tumor can be challenging due to constant changes in cells with metastasis. Conclusion: This is a rare case of endometrial cancer with liver metastasis and ectopic PTH secretion by primary tumor leading to recurrent hospitalizations related to hypercalcemia. Presentation: 6/2/2024

High-grade mucinous tubular and spindle cell carcinoma of the kidney in a patient on hemodialysis: a case report and literature review

BackgroundEnd-stage renal disease is a risk factor for renal cell carcinoma. However, mucinous tubular and spindle cell carcinoma of the kidney is rare. We report a patient on hemodialysis who had high-grade mucinous tubular and spindle cell carcinoma of the kidney.Case presentationA 62-year-old Japanese woman had end-stage renal disease and had been on hemodialysis for the previous 4 years. However, periodic imaging examinations to detect kidney cancer had not been conducted. The patient visited our department of urology complaining of general fatigue and dyspnea. Computed tomography with enhancement revealed a solid renal mass with a diameter of 66 mm. It had invaded the right psoas muscle and had multiple lymph node metastases. In addition, the patient had massive ascites and right-sided predominant pleural effusion. We drained the pleural effusion, but she died 11 days after admission. An autopsy was performed. Pathological examination revealed high-grade mucinous tubular and spindle cell carcinoma of the right kidney; multiple organ metastases to the bilateral lungs, liver, gall bladder, uterus, ovary, and inferior vena cava; cancerous pleuritis; and cancerous peritonitis. Our case indicates that high-grade mucinous tubular and spindle cell carcinoma emerging in end-stage kidney causes a detrimental clinical course.ConclusionHigh-grade mucinous tubular and spindle cell carcinoma of the kidney had a severe clinical course. We recommend periodic screening of patients with end-stage renal disease, using computed tomography or ultrasound.

Uterine carcinosarcomas: A case series of 9 cases from a low-income country.

Uterine carcinosarcomas (UCS) are rare aggressive biphasic tumors classified as a subtype of high-grade uterine carcinomas. However, these tumors have particular histopathological features and clinical behavior with worse prognosis than high-grade uterine carcinomas. The incidence of UCS is increasing and more studies are required to elucidate their clinical and histopathological characteristics. Herein, we report clinicopathological features of 9 cases of UCS in a low-income country. We retrospectively collected all cases of UCS at our Pathology Department over a period of 4 years. The diagnosis was performed on formalin-fixed, paraffin-embedded and hematoxylin and eosin-stained surgical specimens. Nine surgically treated cases of UCS have been registered, representing 12.67% of all uterine malignancies with a mean age of 58.88 years (range: 50-65 years). Abdominal pain and metrorrhagia were the main clinical presentations. The epithelial component of UCS was often a serous carcinoma (66.66%) and patients presented with large tumors (mean size of 9.24 cm, range of 5-19 cm), with advanced FIGO stages (stages III-IV) in 5/9 patients (55.55%). Follow-up data were available in 5/9 patients among which only 2 were alive 2 and 25 months after the surgical treatment (overall survival of 40%). UCS are rare and aggressive uterine tumors with very poor prognosis especially in low-income countries.

Screening of prognostic factors and survival analysis based on histological type for perimenopausal endometrial carcinoma treated with hysterectomy

PurposeThis study aimed to explore the prognostic factors and survival patterns based on the histological type for the perimenopausal endometrial carcinoma (PIPEC) patients treated with hysterectomy.MethodsThe PIPEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Methods of random survival forest (RSF) and Cox regression were used to identify the possible prognostic factors of PIPEC patients. Then overall survival (OS) and cancer-specific survival (CSS) of PIPEC data were analyzed by histological types with regional lymph nodes status and SEER-stage to investigate the survival patterns of the PIPEC patients.ResultsA total of 14,178 PIPEC patients were included in the study. We found tumor size, grade, histology, SEER-stage, AJCC-stage, AJCC-T stage, metastasis to distant organs and regional lymph nodes status had a significant survival outcome for PIPEC both for OS and CSS (all p < 0.05). Regardless of regional lymph nodes status and SEER-stage for OS and CSS, the low-grade endometrioid carcinoma had the best prognosis outcome, followed by the mix cell adenocarcinoma and high-grade endometrioid carcinoma, while the carcinosarcoma and undifferentiated carcinoma had relatively poor prognosis outcome. And the survival patterns of different histological types of PIPEC were diverse and changed along with the time.ConclusionWe identified the possible prognostic factors of PIPEC patients treated with hysterectomy. And survival analysis based on the regional lymph nodes status and SEER-stage revealed the different histological types of PIPEC had diverse survival patterns, which will be helpful for guiding clinical practice.

Clinicopathological Features of CCDC6-RET and NCOA4-RET Fusions in Thyroid Cancer: A Single-Center Retrospective Cohort Study in a Chinese Population.

Background: The rearranged during transfection (RET) proto-oncogene fusion is common in papillary thyroid cancer (PTC), varying across ethnic groups. However, comprehensive comparisons of RET fusion types are limited. This study aims to identify predominant RET fusions and analyze their clinicopathological characteristics in a cohort of Chinese thyroid cancer cases. Methods: This single-center retrospective cohort study analyzed thyroid cancer data, utilizing next-generation sequencing on formalin-fixed, paraffin-embedded tissue samples. Detailed clinicopathological data of thyroid cancer cases with RET fusions were collected. Results: Among 2300 thyroid cancer cases, RET fusions were exclusively found in PTC or differentiated high-grade thyroid carcinoma (DHGTC) cases (2234 cases), absent in other types (66 cases). Of the 2234 PTC or DHGTC cases, 113 (5.06%) exhibited RET fusions, including 100 primary cases. Coiled-coil domain containing 6 (CCDC6)-RET fusions predominated (78.0%, 78/100), with nuclear receptor coactivator 4 (NCOA4)-RET fusions representing 22.0% (22/100). NCOA4-RET fusions were more prevalent in patients aged 45 years and older (54.5% vs. 28.2%, p = 0.021) and DHGTC cases (p < 0.05) and associated with higher rates of lymph node metastases (90.9% vs. 67.9%, p = 0.032). CCDC6-RET fusion exhibited a higher prevalence of Hashimoto's thyroiditis (HT) (67.9% vs. 22.7%, p < 0.001) and elevated thyroglobulin antibody levels (14.11 [1.86-174.32] IU/mL vs. 2.01 [1.14-15.41] IU/mL, p = 0.018). Moreover, CCDC6-RET fusion predominantly occurred in classical PTC (56.4%, 44/78) and infiltrative follicular PTC (17.9%, 14/78), whereas NCOA4-RET fusion was more frequent in classical PTC (36.4%, 8/22), solid PTC (27.3%, 6/22), and DHGTC (27.3%, 6/22). RET fusions with compound mutations were associated with older age (≥45 years) and bilateral thyroid involvement. Follow-up data showed a higher recurrence rate in the RET fusion group compared with the BRAFV600E mutation group (5.0% vs. 0.0%, p = 0.018). Although the NCOA4-RET group showed a numerically higher recurrence rate compared with CCDC6-RET (9.1% vs. 3.8%), this difference was not statistically significant (p = 0.559). Conclusions: RET fusions are specific to PTC or DHGTC cases among Chinese thyroid cancer cases. CCDC6-RET and NCOA4-RET fusions exhibited distinct clinicopathological features, with NCOA4-RET being more aggressive.

Oncologic and Perioperative Outcomes of Robot-Assisted Versus Conventional Laparoscopy for the Treatment of Clinically Uterine-Confined High-Grade Adenocarcinoma.

The aim of this study was to compare oncologic and perioperative outcomes of robot-assisted laparoscopy (RA) and conventional laparoscopy (LSC) in apparent clinically uterine-confined, high-grade adenocarcinoma. A retrospective review was conducted to identify patients with newly diagnosed high-grade uterine adenocarcinoma treated at our institution between 1 January 2009 and 30 June 2021. Exclusion criteria included bulky extrauterine disease, no lymph node assessment, or synchronous tumors. Clinicopathologic details were obtained from medical records. Postoperative complications were classified using the Memorial Sloan Kettering Cancer Center Surgical Secondary Events system, and statistical analysis was performed using appropriate tests. Of 901 patients identified, 748 (83%) underwent RA and 153 (17%) underwent LSC. Median age was 65 years (range 25-92) and median body mass index was 30 kg/m2 (range 15-60). Overall, 650 patients (72%) had 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I disease. Forty-one patients (4.6%) converted to laparotomy-26 (3.5%) from RA versus 15 (9.8%) from LSC (p=0.02). Postoperative complications occurred in 81 patients (9.0%), with no significant differences in type or rate between groups. Median operative time was 192mins (range 88-936) for RA versus 168 mins (range 90-372) for LSC (p=0.002). Median follow-up was 52 months (range 1-163) for RA and 66 months (range 7-165) for LSC. Four-year progression-free survival (PFS) and disease-specific survival (DSS) were similar between groups. Multivariate analysis showed stage, histology, peritoneal cytology, and lymphovascular invasion predicated a decrease in PFS and DSS. RA demonstrated comparable oncologic outcomes to LSC in patients with high-grade endometrial carcinoma, with no significant difference in postoperative complications or long-term survival.

The Simultaneous Use of Bladder Epicheck® and Urinary Cytology Can Improve the Sensitivity and Specificity of Diagnostic Follow-Up of Urothelial Lesions: Up-to-Date Data from a Multi-Institutional Cohort.

Background/Objectives: Bladder cancer is a prevalent urinary system malignancy and urinary cytology is widely used for its screening and follow-up. A novel diagnostic tool called Bladder Epicheck® (BE) is increasingly being used for monitoring the recurrence of non-muscle-invasive bladder cancer (NMIBC). The simultaneous use of BE and urinary cytology can increase the diagnostic performances in the follow-up of bladder neoplasms. Methods: In this multicenter study, we retrospectively evaluated the data of 322 patients in follow-up for a high-grade bladder carcinoma over a six-year period (from January 2018 to March 2024). The diagnostic performances of both cytology and BE and their combination were calculated using histology as gold standard. Results: Recurrences were diagnosed as high-grade urothelial carcinoma NMIBC in 18 cases, low-grade papillary NMIBC in 8 cases, and carcinoma in situ (CIS) in 4 cases. Cytological analysis correctly identified 26 out of 30 carcinomas, while 286 were correctly diagnosed as negative results. BE correctly identified 25 out of 30 carcinomas, 285 were correctly diagnosed as negative results. The combination of BE and urinary cytology correctly identified 29 out of 30 carcinomas, while 289 were correctly diagnosed as negative results. Conclusions: The combination of BE and cytology could be the most effective approach for follow-up diagnosis in patients with high-grade NMIBC, reducing unnecessary invasive procedures.

Histologic and Molecular Type Changes in Endometrial Cancer Recurrences in Comparison With Their Corresponding Primary Tumors.

In this study, molecular alterations in endometrial carcinoma (EC) recurrences were analyzed. We aimed to identify genes implicated in tumor progression and to evaluate whether histologic and molecular type shifting occurs in recurrences. Thus, we analyzed 50 samples corresponding to 24 primary ECs (15 low-grade endometrioid endometrial carcinomas [LG-EECs] and 9 high-grade endometrial carcinomas) and their corresponding 26 recurrences. These were studied by immunohistochemistry, next-generation sequencing, and MLH1 promoter methylation. We observed shared mutations in all primary tumors and their recurrences, indicating a clonal relationship between both lesions. Most morphologic and molecular changes associated with progression were found in LG-EEC. In this group, 6 patients (40%) presented additional mutations in the recurrence. These mutations more frequently affected genes of the PI3K/AKT/PTEN pathway, implicating this pathway not only in tumor initiation but also in progression. In addition, 2 patients (13%) in which the primary tumor belonged to the nonspecific molecular profile subtype, shifted to the mismatch repair deficient (MMRd) subtype after the acquisition of MLH1 promoter methylation in the recurrence lesions. In 3 patients (20%) with MMRd, there was a change from LG-EEC to G3-EEC. One TP53-mutated LG-EEC transformed into an undifferentiated carcinoma in a mediastinal lymph node metastasis after losing the expression of SMARCA2 while preserving SMARCA4 and SMARCB1. Morphologic and molecular changes in EC recurrences, especially dedifferentiation and the acquisition of MMRd, should be considered for a correct diagnosis and treatment. MMRd should be tested in metastatic lesions, if available, in patients with primary tumors reported to be of a molecular subtype different from MMRd.

Prognostic impact of interstitial lung disease on pulmonary high-grade neuroendocrine carcinoma

Pulmonary high-grade neuroendocrine carcinomas (HGNECs) have poor prognoses and require multimodal treatment, and interstitial lung disease (ILD) restricts sufficient treatment of patients with lung cancer. We aimed to clarify ILD’s prognostic impact on pulmonary HGNEC, which has previously gone unreported. We retrospectively analyzed 53 patients with HGNEC who underwent resections at our department between 2006 and 2021 and evaluated the clinicopathological prognostic features, including ILD. The patients’ mean age was 70 years; 46 (87%) were male, and all were smokers. Large-cell neuroendocrine and small-cell lung carcinomas were diagnosed in 36 (68%) and 17 (32%) patients, respectively. The pathological stages were stage I, II, and III in 31 (58%), 11 (21%), and 11 (21%) patients, respectively. Nine patients (17%) had ILD, which was a significant overall survival prognostic factor in a multivariate Cox proportional hazards regression analysis (p = 0.048), along with lymph node metastasis (p = 0.004) and non-administration of platinum-based adjuvant chemotherapy (p = 0.003). The 5 year survival rate of the ILD patients was 0%, significantly worse than that of patients without ILD (58.7%; p = 0.003). Patients with HGNEC and ILD had a poor prognosis owing to adjuvant therapy’s limited availability for recurrence and the development of acute exacerbations associated with ILD.

Double Primary Cancer: Breast Cancer and Gastric Cancer

Introduction: Breast carcinoma is the most prevalent malignancy and the second leading cause of cancer death in women, while multiple primaries are conditions where there is more than one synchronous or metachronous cancer in one individual. Double primary between breast carcinoma and colon cancer is a primary tumor with a high incidence, while breast carcinoma metastasis to the colon is a rare entity except for lobular histotype breast carcinoma. In this case report, a woman with double primary breast cancer is reported. Case Report: A 50-year-old woman came with complaints pain of the entire abdomen since 2 days before go to hospital, worsening when starting to eat, accompanied by nausea. The patient had a history of modified radical mastectomy (MRM) for indications of right breast carcinoma cT3N0M0. In addition, a history of ovarian carcinoma that had undergone chemotherapy was also found. On esophagogastroduodenoscopy examination, a gastric mass was found with ulceration and necrosis and a biopsy showed high-grade neuroendocrine carcinoma and adenocarcinoma. Conclusion: Breast malignancy can be invasive or non-invasive and can undergo metastasis. In addition to metastasis, cancer can also appear in two different places but histologically or morphologically different. This condition is called multiple primaries due to host, lifestyle, and environmental factors.

TERT promoter mutations and additional molecular alterations in thyroid fine-needle aspiration specimens: A multi-institutional study with histopathologic follow-up

Abstract Objectives TERT promoter mutations are not infrequently encountered in thyroid carcinomas; however, it is unclear if additional molecular alterations may play a role in determining tumor behavior. Methods Fine-needle aspiration (FNA) specimens from 32 patients with TERT promoter mutations detected by ThyroSeq v3 from 4 institutions were included in the study. FNA diagnoses, molecular results, and surgical follow-up were retrospectively reviewed and analyzed. Results There were 5 benign and 27 malignant neoplasms, including 7 high-grade thyroid carcinomas (HGCs) on histopathologic follow-up. Of 4 cases with an isolated TERT mutation, 3 (75%) cases were malignant. Of 17 cases harboring a co-occurring TERT mutation with 1 additional molecular alteration, 13 (76%) displayed malignancy on histopathologic follow-up. All 11 cases with TERT mutations plus 2 or more additional molecular alterations were malignant on follow-up. Furthermore, HGC was not seen in cases with an isolated TERT mutation, while 80% of cases harboring TERT mutations plus 3 additional molecular alterations showed HGC. Conclusions TERT promoter mutations are commonly associated with malignancy, particularly HGCs, when multiple co-occurring molecular alterations are present. However, TERT promoter mutations may occasionally be detected in benign thyroid neoplasms when encountered in isolation or with fewer than 2 additional molecular alterations.

EIF1AX mutation in thyroid nodules: a histopathologic analysis of 56 cases in the context of institutional practices.

EIF1AX mutation has been identified as a driver mutation for papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) study. Subsequent studies confirmed this mutation in PTC and Anaplastic Thyroid Carcinoma (ATC) but also reported EIF1AX mutation in Follicular nodular disease (FND) and benign thyroid nodules. In this study, we review thyroid nodules with EIF1AX mutation from two institutions: a tertiary care hospital (YNHH, n = 22) and a major cancer referral center (MSKCC, n = 34) and report the varying histomorphology in the context of additional genetic abnormalities and institutional practices. Pathology diagnoses were reviewed according to the WHO 5th edition and correlated with the type of EIF1AX mutation and additional concurrent molecular alterations, if any. Most cases were splice site type mutations. Cases consisted of 9 FND, 7 follicular (FA) or oncocytic adenomas (OA), 2 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 38 follicular-cell derived thyroid carcinomas. Of 8 cases with isolated EIF1AX mutation, 7 were FND, FA or OA (88%) and one was an oncocytic carcinoma (12%). Of 12 cases with EIF1AX and one additional molecular alteration, 9 (75%) were FND, FA or OA, 2 (17%) were NIFTPs and one (8%) was a poorly differentiated thyroid carcinoma. All 36 cases with EIF1AX mutation and molecular alterations were malignant (100%) and included TP53 and TERT promoter mutations associated with ATC (n = 8) and high-grade follicular cell-derived non-anaplastic carcinoma (HGC, n = 2). Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.

Unusual Scenario: Ipsilateral Pelvic Lymph Node Metastasis in High- Grade Serous Ovarian Carcinoma without Peritoneal Extension - A Case Report

Introduction:: Ovarian cancers are the third most common gynecological cancers worldwide with serous carcinomas being the most common subtype with 90% of them as high-grade carcinomas. Case Presentation:: In the present case report a 60 years postmenopausal, nulliparous woman presented with complaints of bleeding per vaginum for 1-2 months with a left-sided solid-cystic ovarian mass of size 4x5 cm and ipsilateral enlarged external iliac and obturator lymph nodes which were diagnosed on histopathological examination as high-grade serous ovarian carcinoma (HGSOCs) with ipsilateral pelvic lymph node metastasis in presence of intact ovarian capsule and no metastatic deposits over the uterus, contralateral ovary and fallopian tubes, omentum, or any other gross peritoneal deposits. There was coexisting non-atypical endometrial hyperplasia. The patient was managed successfully with staging laparotomy with modified radical hysterectomy, and bilateral pelvic lymphadenectomy followed by six cycles of adjuvant chemotherapy with Paclitaxel and Carboplatin injections. Conclusion:: Patients with HGSOCs can have varied presentations with unusual involvement of lymph nodes in the absence of peritoneal spread. Hence, the clinician must be aware of these unusual presentations for the successful management of such cases.

Efficacy of PD-1/PD-L1 blockade immunotherapy in recurrent/metastatic high-grade neuroendocrine carcinoma of the cervix: A retrospective study

Although high-grade neuroendocrine carcinoma of the cervix (HGNECC) accounts for less than 1 % of all cervical cancers, it exhibits marked aggressiveness and resistance to radiation and chemotherapy. We retrospectively investigated the efficacy of immunotherapy for recurrent/metastatic HGNECC in a real-world setting. From September 2016 to December 2022, a total of 29 patients with HGNECC accepted PD-1/PD-L1 inhibitors; of these, six cases (20.7 %) were PD-L1 positive (combined positive score ≥1). According to their primary treatment, the patients were assigned to either a surgery group (n = 14) or a non-surgery group (n = 15). In the surgery group, four patients received anti-PD-1 therapy immediately after surgery, while six, two, one, and one patients started immunotherapy after the first, second, third, and forth recurrence, respectively. In the non-surgery group, seven patients started immunotherapy as part of their primary treatment, while the other four, two, and two patients received anti-PD-1 drugs as the second, third, and forth lines of treatment, respectively. The seven-patient group showed longer progression-free survival after immunotherapy (PFSi) and overall survival than those of their counterparts (P = 0.085 and 0.08, respectively), while this benefit was not observed in other subgroups. No significant correlation was observed between PD-L1 and PFSi expression. Interestingly, one patient with a high tumor mutation burden (TMB-H) had a long PFSi of 26 months and experienced no recurrence until the last follow-up. Based on these findings, we propose that PD-1/PD-L1 inhibitors may prolong the survival of patients with HGNECC who start immunotherapy as the first-line of treatment. This indicates that early immunotherapy may be a better choice for this challenging malignancy. Moreover, the predictive role of TMB-H in immunotherapeutic outcomes requires further investigation.

Potential of AKNA as a Predictive Biomarker for Ovarian Cancer and Its Relationship to Tumor Grading.

Ovarian cancer exhibits a significant prevalence and incidence on a global scale. Low-grade or high-grade epithelial-type ovarian cancer can be classified by using the dualistic model. Inflammation has been associated with AKNA protein by cancer researchers. The potential of AKNA as a cancer biomarker is supported by its significance and association with ovarian carcinoma. Uninvestigated is this enormous potential. This study examines the correlation between AKNA expression in low-grade and high-grade ovarian tumors and its utility as a predictive biomarker for ovarian cancer. This study examined a total of thirty-one samples, which were classified into three groups: cyst, low-grade, and high-grade ovarian carcinoma. The departmental archive was accessed for the following information: age, tumor size, nuclear grade, mitosis, ovary volume, implant tumor status, lymph vascular invasion status, lymph node metastasis, and tumor-infiltrating lymphocyte. The expression of AKNA was determined using IHC staining. The information was collected and analyzed via analysis of variance. The AKNA H-score shows the mean difference between all three groups (P < 0.001). Cysts had the highest AKNA expression, followed by low-grade and high-grade ovarian carcinoma. Higher-grade ovarian cancer expressed less AKNA compared to cysts or low-grade forms of the disease. This considerable difference suggests that AKNA might predict ovarian cancer tumor grade.

901P A phase II trial of neoadjuvant nivolumab, docetaxel, and cisplatin therapy followed by surgery and radiation therapy for resectable high-grade salivary gland carcinoma

901P A phase II trial of neoadjuvant nivolumab, docetaxel, and cisplatin therapy followed by surgery and radiation therapy for resectable high-grade salivary gland carcinoma

52048 Radiologic imaging aids management of high-grade cutaneous squamous cell carcinoma (cSCC)

52048 Radiologic imaging aids management of high-grade cutaneous squamous cell carcinoma (cSCC)

1788P Final overall survival analysis of JCOG1205/1206: Phase III study of irinotecan/cisplatin (IP) versus etoposide/cisplatin (EP) for completely resected high-grade neuroendocrine carcinoma (HGNEC) of the lung

1788P Final overall survival analysis of JCOG1205/1206: Phase III study of irinotecan/cisplatin (IP) versus etoposide/cisplatin (EP) for completely resected high-grade neuroendocrine carcinoma (HGNEC) of the lung

Molecular classification of ovarian high-grade serous/endometrioid carcinomas through multi-omics analysis: JGOG3025-TR2 study.

Considerable interobserver variability exists in diagnosis of ovarian high-grade endometrioid carcinoma (HGEC) and high-grade serous carcinoma (HGSC) due to histopathological similarities. While homologous recombination deficiency (HRD) correlates with drug sensitivity in HGSC, the molecular features of HGEC are unclear. Fresh-frozen samples from 15 ovarian HGECs and 274 ovarian HGSCs in the JGOG-TR2 cohort were submitted to targeted DNA sequencing, RNA sequencing, DNA methylation array, and SNP array. We additionally analyzed 555 ovarian HGSCs from TCGA-OV and 287 endometrial high-grade carcinomas from TCGA-UCEC. Unsupervised clustering using copy number signatures identified four distinct tumor groups (C1, C2, C3 and C4). C1 (n = 41) showed CCNE1 amplification and poor survival. C2 (n = 160) and C3 (n = 59) showed high BRCA1/2 alteration frequency with low and moderate ploidy, respectively. C4 (n = 22) was characterized by favorable outcome, higher HGEC proportion, no BRCA1/2 alteration or CCNE1 amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, and WT1 gene expression. Notably, C4 exhibited a normal endometrium-like DNA methylation profile, thus, defined as "HGEC-type" tumors, which were also identified in TCGA-OV and TCGA-UCEC. Ovarian "HGEC-type" tumors present a non-HRD status, favorable prognosis, and endometrial differentiation, possibly constituting a subset of clinically diagnosed HGSCs.

Direct DNA binding by BRCA1 on β-hCG promoter and its clinical implications

ObjectiveThe role of β-hCG in breast cancer is largely unknown, this study aims to analyse the gene expression and clinical implications of β-hCG and its isoforms in various cancers focussing particularly in Breast Invasive Carcinoma (BRCA). A mechanistic approach deciphering the transcriptional regulation of β-hCG by BRCA1 was also explored. MethodsData from various comprehensive gene expression platforms like UALCAN, GEPIA2, GENT2, TIMER2, LinkedOmics, and STRING were used to analyse the expression of β-hCG and its clinical implications; Immunohistochemistry and ELISA for β-hCG expression analysis from human breast cancer patients; Electrophoretic mobility shift assay (EMSA) to analyse the direct binding of BRCA1 on β-hCG; Immunoblotting and Luciferase assay to understand the regulation of β-hCG by p53 were performed. ResultsResults from UALCAN and GENT2 gene expression cancer database revealed that TNBC subtypes and high-grade metaplastic carcinoma shows elevated expression of β-hCG and infiltration of various immune cells were also identified in BRCA by TIMER2. It was observed that most of the isoforms of β-hCG (CGB) are upregulated in breast cancers irrespective of hormonal status when BRCA1 gene is mutated according to TIMER2. Similar results were observed with Lymphoid neoplasm diffuse large B-cell lymphoma (LGG) and DLBC (Brain lower grade glioma) when BRCA1 is mutated. These results correlate with our earlier reports indicating expression of β-hCG in BRCA1 defective condition. We have also identified direct binding of BRCA1 on β-hCG promoter. ConclusionAll these findings demonstrate the importance of β-hCG as a potential target in BRCA1-deficient carcinomas.