Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST.

OBJECTIVE: We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. METHODS: We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. RESULTS: Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3-189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3-54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. CONCLUSION: Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST.

Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.

Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that mainly harbors NCOA1-3 rearrangements with partner genes ESR1 or GREB1 . Here, we explored 23 UTROSCTs by targeted RNA sequencing. The association between molecular diversity and clinicopathologic features was investigated. The mean age of our cohort was 43 years (23-65 y). Only 15 patients (65%) were originally diagnosed with UTROSCTs. Mitotic figures ranged from 1 to 7/10 high power fields, of primary tumors and increased from 1 to 9/10 high power fields in recurrent tumors. Five types of gene fusions were identified in these patients, including GREB1::NCOA2 (n=7), GREB1::NCOA1 (n=5), ESR1::NCOA2 (n=3), ESR1::NCOA3 (n=7), and GTF2A1::NCOA2 (n=1). To our knowledge, our group included the largest cohort of tumors with GREB1::NCOA2 fusions. Recurrences were most common in patients with GREB1::NCOA2 fusion (57%), followed by 40% ( GREB1::NCOA1 ), 33% ( ESR1::NCOA2 ), and 14% ( ESR1::NCOA3 ). The recurrent patient who harbored an ESR1::NCOA2 fusion was characterized by extensive rhabdoid features. Both of the recurrent patients who harbored GREB1::NCOA1 and ESR1::NCOA3 had the largest tumor sizes in their own gene alteration groups, and another recurrent GREB1::NCOA1 patient had extrauterine involvement. The GREB1 -rearranged patients were of older age, larger tumor size, and higher stage than non- GREB1 -rearranged patients ( P =0.004, 0.028, and 0.016, respectively). In addition, the GREB1 -rearranged tumors presented more commonly as intramural masses rather than non- GREB1 -rearranged tumors presenting as polypoid/submucosal masses ( P =0.021). Microscopically, nested and whorled patterns were frequently seen in GREB1- rearranged patients ( P =0.006). Of note, estrogen receptor expression was weaker than progesterone receptor in all 12 GREB1- rearranged tumors, whereas the similar staining intensity of estrogen receptor and progesterone receptor was observed in all 11 non- GREB1- rearranged tumors ( P <0.0001). This study demonstrated that UTROSCTs were present at a younger age in the Chinese population. The genetic heterogeneity of UTROSCTs was correlated with variable recurrence rate. Tumors with GREB1::NCOA2 fusions are more likely to recur compared with those with other genetic alterations.

Head-to-head comparison of [18F]-FDG and [68 Ga]-DOTA-FAPI-04 PET/CT for radiological evaluation of platinum-sensitive recurrent ovarian cancer.

PURPOSE: Precise radiological evaluation is pivotal for the management of platinum-sensitive recurrent ovarian cancer. We aimed to compare the value of [68 Ga]-FAPI and [18F]-FDG PET/CT for the detection of relapsed lesions. METHODS: Twenty-nine suspected platinum-sensitive recurrent ovarian cancers were enrolled from January 2022 to July 2022. [18F]-FDG and [68 Ga]-FAPI PET/CT were obtained within 1 week for radiological evaluation. Treatment strategies, visual scores, and Eisenkop scores were recorded. A paired T test was used to compare differences between two scans. Sensitivity, specificity, PPV, NPV, and accuracy were also evaluated. RESULTS: Up to 22 (75.86%) patients displayed inconsistency between two scans. Among them, 4 patients with negative [18F]-FDG imaging had measurable lesions in [68 Ga]-FAPI scans. The treatment strategies were changed in 5 patients (17.24%) due to discrepancies. Finally, 15 (35.7%) patients underwent surgeries, and 14 patients achieved complete resection, except for 1 patient who had milliarc residual disease. TBR, but not SUVmax, of [68 Ga]-FAPI was significantly higher than that of [18F]-FDG in recurrent lesions. Compared with [18F]-FDG, [68 Ga]-FAPI PET presented higher sensitivity and accuracy for lesion detection (96.30% vs. 49.07% and 97.40% vs. 63.87%, respectively). Additionally, [68 Ga]-FAPI PET showed a much higher visual score than [18F]-FDG PET (41 vs. 4), especially for peritoneal metastasis (35 vs. 1). [68 Ga]-FAPI PET also presented a larger tumor burden than [18F]-FDG according to the Eisenkop score (27 vs. 16, p = 0.025). CONCLUSIONS: [68 Ga]-FAPI was superior to [18F]-FDG PET/CT for the detection of recurrent lesions, which is pivotal for the individualized management of platinum-sensitive recurrent ovarian cancer.

Neoadjuvant chemotherapy followed by radical trachelectomy versus upfront abdominal radical trachelectomy for patients with FIGO 2018 stage IB2 cervical cancer.

OBJECTIVE: To explore the optimal fertility-sparing treatment for stage IB2 cervical cancer. We compared the outcomes of neoadjuvant chemotherapy (NACT) followed by radical trachelectomy (RT) with those of upfront abdominal RT (ART). METHODS: This is a retrospective study with prospectively collected data between August 2015 and July 2019. Patients with IB2 cervical cancer who desired fertility preservation underwent NACT followed by RT, or upfront ART, per their choice. RESULTS: This study included 51 patients, of which, 16 patients underwent NACT followed by RT and 35 patients chose upfront ART. Fertility was preserved in 12 (75.0%) and 27 (77.1%) patients from the NACT and upfront ART groups, respectively. Incidence rates of intraoperative (0% versus 3.7%) and postoperative complications (25.0% versus 48.1%) of the NACT group were lower compared to the upfront ART group (P=NS). Eleven (91.7%) patients in NACT group and 17 (63.0%) patients in upfront ART groups received adjuvant chemotherapy after surgery. The median follow-up, and 5-year recurrence-free survival rates of the NACT-RT and upfront ART groups were 56 and 61 months, and 83.3% and 96.3%, respectively (P=NS). The recurrence rate was higher in patients with tumor reduction <50% after NACT than that in patients with tumor reduction >50% (66.7% versus 0%, P < 0.05). Tumor reduction <50% was the only independent predictor of recurrence in patients who underwent NACT before RT. CONCLUSIONS: NACT followed by RT could be a feasible fertility-sparing option for selected patients with 1B2 cervical cancer. The NACT group had a relatively higher recurrence rate and fewer complications compared to the upfront ART group, albeit without statistical significance. Patients with tumor regression >50% after NACT could be ideal candidates for RT after NACT.

Diffusion-Weighted Magnetic Resonance Imaging and Morphological Characteristics Evaluation for Outcome Prediction of Primary Debulking Surgery for Advanced High-Grade Serous Ovarian Carcinoma.

BACKGROUND: Preoperative assessment of whether a successful primary debulking surgery (PDS) can be performed in patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains a challenge. A reliable model to precisely predict resectability is highly demanded. PURPOSE: To investigate the value of diffusion-weighted MRI (DW-MRI) combined with morphological characteristics to predict the PDS outcome in advanced HGSOC patients. STUDY TYPE: Prospective. SUBJECTS: A total of 95 consecutive patients with histopathologically confirmed advanced HGSOC (ranged from 39 to 77 years). FIELDS STRENGTH/SEQUENCE: A 3.0 T, readout-segmented echo-planar DWI. ASSESSMENT: The MRI morphological characteristics of the primary ovarian tumor, a peritoneal carcinomatosis index (PCI) derived from DWI (DWI-PCI) and histogram analysis of the primary ovarian tumor and the largest peritoneal carcinomatosis were assessed by three radiologists. Three different models were developed to predict the resectability, including a clinicoradiologic model combing MRI morphological characteristic with ascites and CA125 level; DWI-PCI alone; and a fusion model combining the clinical-morphological information and DWI-PCI. STATISTICAL TESTS: Multivariate logistic regression analyses, receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI) were used. A P < 0.05 was considered to be statistically significant. RESULTS: Sixty-seven cases appeared as a definite mass, whereas 28 cases as an infiltrative mass. The morphological characteristics and DWI-PCI were independent factors for predicting the resectability, with an AUC of 0.724 and 0.824, respectively. The multivariable predictive model consisted of morphological characteristics, CA-125, and the amount of ascites, with an incremental AUC of 0.818. Combining the application of a clinicoradiologic model and DWI-PCI showed significantly higher AUC of 0.863 than the ones of each of them implemented alone, with a positive NRI and IDI. DATA CONCLUSIONS: The combination of two clinical factors, MRI morphological characteristics and DWI-PCI provide a reliable and valuable paradigm for the noninvasive prediction of the outcome of PDS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Clinicopathological and molecular characteristics of fumarate hydratase-deficient uterine smooth muscle tumors: a single-center study of 52 cases.

The fumarate hydratase (FH) gene germline mutations cause hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), predisposing carriers to uterine and cutaneous leiomyomas and renal cell carcinoma. In this study, we aim to investigate morphology and the correlation between FH mutation in FH-deficient (FH-d) uterine smooth muscle tumors (uSMTs). We conducted immunohistochemical staining in 161 cases of uSMTs to detect FH deficiency. We identified 52 cases (52/161, 32%) of FH-d, including 34 leiomyomas with bizarre nuclei, 10 uSMTs of uncertain malignant potential (STUMPs), 4 cellular leiomyomas, 3 usual type leiomyomas, and 1 leiomyosarcoma. Patients with FH-d were aged 24-67 years (median, 40 years). The most common FH-d morphological features included staghorn-shaped blood vessels (87%), bizarre nuclei (81%), alveolar pattern edema (65%), macronucleoli surrounded by a halo (65%), cytoplasmic eosinophilic globules (56%), and chain-like distribution of smooth muscle cells (52%). A targeted next-generation sequence was performed in 11 of 52 FH-d tumors. Five cases (5/11, 45%) were found with FH germline mutations, including 4 leiomyomas with bizarre nuclei and 1 STUMP. The median age of patients with germline FH mutation was 30 years. The germline mutations included 3 pathogenic, 1 likely pathogenic, and 1 rare uncertain clinical significance variants. Our results revealed that FH-d uSMTs usually exhibit the distinct morphology features and high frequency of FH germline mutations. The combination of predictive morphology evaluation, FH immunotype, and molecular testing is helpful for the screening of HLRCC in uSMTs.

Comprehensive quantitative malignant risk prediction of pure grouped amorphous calcifications: clinico-mammographic nomogram.

Background: Pure grouped amorphous calcifications are classified as Breast Imaging Reporting and Data System (BI-RADS) category 4B suspicious calcifications and recommended for biopsy. However, the biopsies often reveal benign findings, especially in screening mammograms (92.4-97.2%). Methods: Mammograms of 699 pure grouped amorphous calcifications with final pathological results were analyzed in this retrospective study. The maximum span (MS) of the group of calcifications and the MS of the parallel/vertical direction of the mammary duct (MPS/MVS) were measured, and the MPS to MVS ratio was calculated. Based on the MS and ratio, 2 prediction nomograms with other clinic-mammographic features were developed. The discrimination performance of the models was assessed and compared by the area under the receiver operating characteristic curve (AUC). Scatterplots were created to determine the cutoff values with fewer misdiagnoses of malignant calcifications and fewer false positives. Results: Ultimately, 2 prediction models were successfully developed based on the 4 risk factors of age, purpose of the mammogram, whether multiple or single calcifications, and the MS [odds ratio (OR) =1.06, P=0.02]/ratio (OR =6.05, P<0.001). Both models had good discrimination. The ratio model performed better than the MS model in the training cohort (AUC of 0.875 and 0.834, respectively, P=0.003) and validation cohort (AUC 0.908 and 0.867, respectively, P=0.047). For the group with probably benign calcifications (as detected by the ratio nomogram), the malignancy rates were 2.7% [95% confidence interval (CI): 1.00% to 6.53%] and 1.19% (95% CI: 0.06% to 7.37%) in the training and validation cohorts, respectively, and 44.12% and 47.70% of benign biopsies were detected in the training and validation cohorts, respectively. Conclusions: The clinico-mammographic quantitative malignancy risk prediction nomogram showed favorable discrimination and calibration performance. The ratio model showed better diagnostic efficiency than the MS model, and identified >40% of benign biopsies.

Pure primary yolk sac tumor of the endometrium tends to occur at a younger age: A case report and literature analysis.

We present a case of primary yolk sac tumor of the endometrium. This rare tumor occurred in a 43-year-old woman with a pure primary yolk sac tumor. The tumor resembled yolk sac tumor morphology of the ovary. Tumor cells expressed SALL4, AFP, GPC-3, and AE1/AE3 and were focal positive for PAX8. EMA, ER, and PR, among others, were negative. We further analyzed 29 reported cases of this rare tumor in the literature. In total, 17 of 30 patients (57%) had pure endometrial yolk sac tumor, and 13 (43%) had a concomitant somatic neoplasm (endometrial adenocarcinoma was the most common). Although the average age was 52 years (range: 24-87 years), patients with pure yolk sac tumor were younger than those with concomitant somatic tumors, with a mean age of 44.41 years (24-68 years) versus 61.92 years (28-87 years), P = 0.008. Patients with endometrial yolk sac tumor combined with somatic tumor tend to have a slightly higher stage and a poor prognosis.

Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency. METHODS: A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays. RESULTS: dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %). CONCLUSIONS: Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.

Prognostic and predictive values of the KIT11-mutated grading system in patients with gastrointestinal stromal tumors: a retrospective study.

The KIT11 mutation is the most frequent mutation pattern in gastrointestinal stromal tumors (GISTs). However, few studies have investigated the correlation between the KIT11-mutated grading system and imatinib mesylate (IM) sensitivity (the first choice for adjuvant treatment of GISTs). Here, we elucidated the clinical value of the KIT11-mutated grading system for prognostic prediction in patients with GISTs treated with IM. A total of 106 patients with GIST were treated with IM (8: intermediate-risk, 98: high-risk; 10: KIT9-mutated, 86: KIT11-mutated, 5: wild-type, and 5: other mutations). KIT11-mutated patients were divided into 3 grades based on the KIT11-mutated site and type. Clinical backgrounds and prognostic outcomes were retrospectively compared between the 3 groups. Of 86 KIT11-mutated patients treated with IM, 32 (37.21%) had grade 1 tumors, 37 (43.02%) had grade 2 tumors, and 17 (19.77%) had grade 3 tumors. The 5-year disease-free survival (DFS) was significantly worse in patients with grade 3 KIT11-mutated GISTs (41.96%, p = 0.001) than in those with grade 1 (93%) and grade 2 (70.64%) cases. The multivariable analysis suggested that the KIT11-mutated grading system was an independent risk factor for DFS in patients treated with IM (hazard risk, 2.512; 95% confidence interval, 1.370-4.607; p = 0.003). In conclusion, the KIT11-mutated grading system provides good prognostic stratification for DFS in patients treated with IM. Grade 1 tumors predict a favorable response to IM.

A novel 2-deoxy-2-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT)-based nomogram to predict lymph node metastasis in early stage uterine cervical squamous cell cancer.

BACKGROUND: We aimed to establish an effective 2-deoxy-2-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) based nomogram for pelvic lymph node (PLN) metastasis prediction in early-stage uterine cervical squamous cell cancer. METHODS: A predictive model was developed in a cohort that consisted of 351 patients with stage IB-IIA [International Federation of Gynecology and Obstetrics (FIGO) 2009] uterine cervical squamous cell cancer. All patients underwent a preoperative PET/CT scan and subsequent radical surgery between 2010 and 2017, with 241 and 110 patients allotted into training and external validation cohorts. The chi-square (χ2) test and the logistic regression analysis were used to compare the clinical and PET/CT parameters with PLN metastasis. A nomogram was developed and validated by internal and external validation. RESULTS: In the training cohort, 82 (34.0%) patients had positive PLNs identified in the preoperative PET/CT scan. Among them, 46 (56.1%) were pathologically confirmed. There were 30 (18.9%) PET/CT scan-negative patients found to have PLN metastasis. The χ2 test and logistic regression showed that only the squamous cell carcinoma antigen (SCCA) level (P=0.039) and maximum standardized uptake value (SUVmax) of PLN (nSUVmax, P=0.001) were independent predictors for PLN metastasis. A predictive nomogram based on these 2 parameters was developed with a C-index [95% confidence interval (CI)] of 0.854 (0.772-0.937) on internal validation and 0.836 (0.723-0.948) on the external validation. Compared to nSUVmax alone, our nomogram showed elevated sensitivity (70.5%, 73.1% vs. 60.5%), specificity (94.4%, 86.4% vs. 78.2%), and positive predictive value (PPV) (93.9%, 86.4% vs. 56.1%) in both the training and validation cohorts. CONCLUSIONS: We successfully developed a noninvasive and convenient nomogram for preoperative identification of PLN metastasis in early-stage squamous cell cervical cancer.

Recurrent uterine tumors resembling ovarian sex-cord tumors with the growth regulation by estrogen in breast cancer 1-nuclear receptor coactivator 2 fusion gene: a case report and literature review.

BACKGROUND: Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are rare mesenchymal neoplasms predominantly arising in perimenopausal and postmenopausal women. UTROSCTs with growth regulation by estrogen in breast cancer 1 (GREB1)-rearrangement or GREB1-rearranged uterine tumors are exceptionally rare, with only 12 previously reported cases. Here, we report a case of UTROSCT with the GREB1-nuclear receptor coactivator 2 (NCOA2) fusion gene. CASE PRESENTATION: A 57-year-old woman presented with a 10.0 cm uterine mass. The tumor was composed of short spindle or epithelioid cells, arranged in diffused sheets, nested, and trabecular/cordlike. The tumor harbored the GREB1-NCOA2 fusion gene, as confirmed by RNA sequencing. The tumor recurred in the pelvis at 30 months after the initial diagnosis. We also compared the clinical and pathologic features of this case with those of the 12 previously published uterine GREB1-rearranged tumors. Of the combined 13 cases (present case and 12 previous cases), the mean age of patients was 64.8 years (range, 51-74 years). Of the nine reported cases of GREB1-rearranged tumor with follow up, four cases recurred or metastasized (44.4%). Microscopically, most tumors (10/12, 83.3%) showed infiltrative growth, and two were well demarcated. Mitotic figures ranged from 0 to 14 per 10 high-power fields (2 mm2; mean: 3.6). Lymphovascular invasion and necrosis were each present in two cases (2/12, 16.7% and 2/7, 28.6%, respectively). CONCLUSIONS: This case provided further evidence that UTROSCTs with GREB1-rearrangement may have a high risk of recurrence/metastasis. Further studies are necessary to clarify the clinical features of this type of tumor, particularly the prognosis, potential treatment, and range of possible molecular events.

The feasibility of 18F-FDG PET/CT for predicting pathologic risk status in early-stage uterine cervical squamous cancer.

BACKGROUND: Postoperative pathologic risk factors (PRFs) could increase the recurrence rate in early-stage uterine cervical squamous cancer (ECSC). Our study intended to explore the efficiency of 18F-FDG PET/CT for assessing the pathologic risk status (PRS) in ECSC patients. METHODS: This retrospective study was performed in 240 ECSC patients with stage IA2-IIA2 (FIGO 2009), who underwent preoperative PET/CT scans and subsequent radical surgery between January 2010 and July 2015. Intermediate-risk (tumour diameter ≥ 4 cm, stromal invasion depth ≥ 1/2, lymphovascular space invasion (LVSI)), and high-risk factors (parametria involvement, positive surgery margin, pelvic lymph node metastasis) were confirmed by postoperative pathology. Patients with none of these PRFs were at a low risk for relapse. One of these PRFs was defined as positive risk. The relationship between each PRF and 18F-FDG uptake was analysed by t-test. Chi-square tests and logistic regression analyses were used to determine the efficiency of PET/CT parameters for assessing the PRS. The area under the curve (AUC) was used as an indicator for predictive efficiency. RESULTS: Patients with higher SUVmax (p < 0.001), MTV (p < 0.001) and TLG (p < 0.001) had larger tumour sizes and deeper stromal invasion. Further multivariate analyses showed SUVmax and TLG were independent predictors for positive- and intermediate-risk status. In high-risk group, MTV and TLG were associated with pelvic lymph node metastasis and parametria involvement. However, only MTV was a significant indicator. CONCLUSIONS: Preoperative 18F-FDG PET/CT had an independent predictive value for PRS in ECSC.

Preoperative PET/CT score can predict complete resection in advanced epithelial ovarian cancer: a prospective study.

BACKGROUND: To assess the ability of preoperative positron emission tomography/computed tomography (PET/CT) scans to predict postoperative residual disease in advanced epithelial ovarian cancer (AEOC). METHODS: Thirty-one women with suspected AEOC were enrolled in our prospective study before surgery from July 2016 to December 2017. Complete resection was determined as no residual disease (R0) after surgery. A PET/CT scan was obtained within 2 weeks before surgery in our hospital. The PET score was the sum of each score of the radiological criteria from Suidan's model. The correlations between the PET score and tumor burden and surgical complexity were evaluated by Pearson correlation analysis. T-test or Fisher's exact test was used to compare differences in the variables between the complete and incomplete resection groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the PET score for predicting complete postoperative resection. RESULTS: The median [range] of PET score was 2 [0-8], and the PET score in 20 (65%) patients was less than 3. Complete resection was achieved in 11 (35.5%) patients after surgery, including 10 (90.91%) with low PET scores and only 1 (9.09%) with a high score. The PET score had a significant positive correlation with tumor burden [Eisenkop: r=0.603, P<0.001; peritoneal cancer index (PCI): r=0.522, P=0.003] but not with surgery complexity (Aletti: r=0.291, P=0.113). Patients with lower PET scores (P=0.046) and tumor burdens (Eisenkop: P=0.013; PCI: P=0.012) had higher rates of complete resection. The PET score and tumor burden were effective for predicting complete resection. The AUCPET, AUCEisenkop, and AUCPCI were 0.797 (95% CI: 0.633-0.961, P=0.01), 0.847 (95% CI: 0.707-0.988, P=0.003), and 0.811 (95% CI: 0.653-0.969, P=0.007), respectively. However, surgery complexity was not useful for assessing complete resection. CONCLUSIONS: The preoperative PET score can noninvasively reflect tumor burden and helps predict complete resection after surgery in AEOC patients.

ALK rearrangement: a high-frequency alteration in ovarian metastasis from lung adenocarcinoma.

BACKGROUND: Ovarian metastatic tumors from lung adenocarcinoma are rare, and a serial study of these tumors is lacking to date. Additionally, a better understanding of the clinicopathological and molecular characteristics of metastatic tumors is needed. METHODS: Seven cases of ovarian metastasis from lung adenocarcinoma from 2013 to 2017 at our institute were investigated. The results were combined with those found in literature review. A total of 16 cases were analyzed in the present study. We examined clinicopathological and immunohistochemical characteristics, further detected ALK rearrangement by FISH (fluorescence in situ hybridization), and assessed EGFR and KRAS mutations using Sanger sequencing or the amplification refractory mutation system (ARMS). RESULTS: The mean age of the patients was 44.6 years (range, 33-56 years). Eleven of sixteen patients developed ovarian tumors within a mean time of 18.5 months (range, 5-48 months) from the initial diagnosis of lung adenocarcinoma; 5 patients had lung tumors and ovarian masses simultaneously. Five tumors (5/16, 31%) occurred in the bilateral ovaries, and the others were unilateral ovarian tumors (11/16, 69%). All seven cases from our institute were positive for TTF-1 and Napsin A but negative for PAX8. In four cases, ALK (D5F3) was diffusely and strongly expressed, with ALK rearrangements (4/7, 57%). Overall, ALK rearrangement was found by FISH or immunohistochemistry in 11/16 (69%) cases. In two cases, EGFR mutations in exons 19 and 21, respectively, were found. One patient did not detected EGFR or ALK mutation in the metastatic tumor, but the primary lung adenocarcinoma did harbor an EGFR mutation. Two cases had no alterations in three genes above. Although the mean survival time of the patients with ALK rearrangement was longer than those without (mean survival time 25 m vs. 20 m), no statistical significance of the difference was found. CONCLUSIONS: As the largest case series of ovarian metastasis from lung adenocarcinoma, our findings indicate that ALK rearrangement is the most common molecular alteration. Although patients with ALK rearrangement appear to have a better prognosis than do those without ALK rearrangement, more cases with longer follow-up and multivariant analysis are needed to clarify this point.

LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p.

Recently, the long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogenic gene in multiple human tumor entitles, and dysregulation of UCA1 was tightly linked to carcinogenesis and cancer progression. However, whether the aberrant expression of UCA1 in non-small cell lung cancer (NSCLC) is associated with malignancy, metastasis or prognosis has not been characterized. In this study, we found that UCA1 was upregulated in NSCLC tissues. Higher expression of UCA1 led to a significantly poorer survival time, and multivariate analysis revealed that UCA1 was an independent risk factor of prognosis. UCA1 overexpression enhanced, whereas UCA1 silencing impaired the proliferation and colony formation of NSCLC cells. Moreover, mechanistic investigations showed that UCA1 upregulated the expression of miR-193a-3p target gene ERBB4 through competitively 'spongeing' miR-193a-3p. Overall, we concluded that UCA1 functions as an oncogene in NSCLC, acting mechanistically by upregulating ERBB4 in part through 'spongeing' miR-193a-3p.

A new method of surgical margin assuring for abdominal radical trachelectomy in frozen section.

OBJECTIVES: The aim of this study was to introduce a new method of assuring surgical margins for abdominal radical trachelectomy (ART) and report our experience using the method. METHODS: We combined transverse and perpendicular sections to assess surgical margins of specimens from RT. All surgeries from 1st August 2012 to 1st October 2013 were performed by one surgeon. The frozen section (FS) was consistently performed by a group of gynaecologic pathologists according to the detailed protocol described in this article. All cases were prepared by the same pathologist, and the slides were reviewed by two pathologists. RESULTS: There were 53 patients treated using the new method in our institution. The patient ages ranged from 20 to 41 years old (median 32). The surgeries were performed for clinical stage IA (n = 11) with LVSI and IB (n = 42) tumours (40 squamous cell carcinoma, 11 adenocarcinoma, two adenosquamous and two others). In 20 (37.74%) cases, no residual tumour of the ART specimen on frozen section was observed in the specimens as it was cleared by the preceding loop electrical excision procedure (LEEP) or conization. The margins were initially reported as negative in 45 cases and positive in nine cases. In those nine cases, a second slice of cervix was removed and negative in six cases and positive again in two cases, the other one with positive nodes. The results of frozen sections were concordant with the final paraffin-embedded sections. There were no false negative intraoperative assessments. There were no recurrences after a median follow-up of 15.4 months (range, 6-21 months). CONCLUSIONS: Combining transverse and perpendicular sections to assess surgical margins of specimens from RT makes the protocol simple, reliable and produces accurate results.

Surgical and pathological outcomes of abdominal radical trachelectomy versus hysterectomy for early-stage cervical cancer.

OBJECTIVES: The aim of this study was to compare the surgical and pathological outcomes for patients with early-stage cervical cancer after abdominal radical trachelectomy (ART) and abdominal radical hysterectomy (ARH). METHODS: A prospective database of ART and ARH procedures performed in a standardized manner by the same surgical group was analyzed. The 3-segment technique was used for the accurate analysis of parametrial lymph nodes (PMLNs), and parametrial measurements were recorded by the same pathologist. Standard statistical tests were used. RESULT: Between August 2012 and August 2013, ART was attempted in 39 patients (28.6%), and ARH was attempted in 90 patients (71.4%). The parametrium resection length was similar with ART and ARH (44.60 vs 45.48 mm, P = 0.432), as were additional surgical and pathological outcomes, including histology, lymph node positive rate, and operation time. The PMLNs were found in 28 patients (77.78%) in the ART group and in 86 (95.56%) in the ARH group (P > 0.05). Solitary PMLN metastases were observed in 3 patients (10.71%) in the ART group and in 6 (6.98%) in the ARH group. Five (55.6%) of these 9 patients had tumors of 2 cm or greater. The ARH patients (36, 40.00%) were more likely to receive postoperative chemotherapy or radiation compared with ART patients (13, 33.33%; P = 0.017). At a median follow-up of 12 and 12.5 months (P = 0.063), respectively, there were no recurrences or deaths in the ART or ARH groups. CONCLUSIONS: Using standardized techniques, ART provides similar surgical and pathological outcomes as ARH. For the patients with tumors of 2 cm or greater, PMLNs should be examined carefully. Further prospective data are urgently needed.

Adenomatous polyposis coli determines sensitivity to the EGFR tyrosine kinase inhibitor gefitinib in colorectal cancer cells.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat colorectal cancer (CRC). However, resistance to EGFR-TKIs presents a great challenge for the treatment of CRC, and the mechanisms of resistance are poorly understood. The adenomatous polyposis coli (APC) protein has been known to contribute to the carcinogenesis of CRC. However, its role in the sensitivity of CRC cells to gefitinib has not been investigated. Human CRC HCT-116 (wild-type APC) and HT-29 (mutant APC) cells were used to investigate the effect of APC on the sensitivity of CRC cells to gefitinib. The MTT assay was used to measure cell viability after exposure to gefitinib. Cell apoptosis, migration and invasion were determined by flow cytometry, wound healing assay and transwell assay, respectively. Knockdown and overexpression of APC were performed, and activation of the EGFR and its downstream pathway was determined. Gefinitib inhibited viability, promoted apoptosis, and reduced the migration of HCT-116 and HT-29 cells. HT-29 cells exhibited increased sensitivity to gefinitib when compared to HCT-116 cells. Knockdown of APC expression increased the sensitivity of HCT-16 cells to gefitinib, accompanied by downregulation of pEGFR, p-AKT and pERK1/2. In contrast, overexpression of APC decreased the sensitivity of HT-29 cells to gefitinib, accompanied by upregulation of pEGFR, p-AKT and pERK1/2. APC plays an important role in the sensitivity of CRC cells to gefitinib. APC may represent a potential therapeutic target for the treatment of CRC.