Early Distant Metastasis Research Articles

Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma: clinical and prognostic implications.

HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis –PSC- above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument.

Investigating the prognostic value of KOC (K homology domain containing protein overexpressed in cancer) overexpression after curative intent resection of pancreatic ductal adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer mortality in the United States. More than 80% of patients present with distant metastasis precluding surgical eligibility. Even among patients with localized disease deemed eligible for surgical resection, the median survival is only 22.8 months due to high recurrence rates. Identification of a biomarker correlated with patient specific prognosis upon initial diagnosis can serve as a way to individualize treatment options. We performed a retrospective cohort study analyzing pathology of patients who underwent curative intent surgery for PDAC at Geisinger Medical Center from 1998-2011 to identify whether the expression of KOC can be predictive of patient specific prognosis. Tissue microarrays of specimens were assessed by immunohistochemistry. A total of 62 patients are included. Comparisons between groups on overall survival (OS) and progression free survival (PFS) are estimated using the Kaplan-Meier method and the log-rank test. Each biomarker was represented as low and high expression by categorizing the expression score at <4+ or >4+, based on intensity and extent of cells stained. 40 deaths occurred in the sample. Distant metastasis and differentiation (well/moderate vs. poor) were related to OS (P=0.0120, P=0.0086). Twenty-nine patients progressed in their disease. High/low KOC expression were significantly related to PFS (P=0.0556). Patients with a high KOC expression were more than 2 times more likely to progress compared to those with a low KOC expression (HR =2.04; 95% CI: 0.97, 4.29). Our data is suggestive of KOC being a useful prognostic biomarker for identifying those patients with PDAC who have a high risk for early progression and distant metastasis. Larger studies are needed to determine whether KOC can be a therapeutic target in the treatment of pancreatic cancer. Furthermore, considering high KOC expressers had a worse PFS than their counterparts, investigation regarding the use of KOC expression as a biomarker to preselect patients who may benefit most from neoadjuvant chemotherapy is warranted.

Anorectal malignant melanoma: curative abdominoperineal resection: patient selection with 18F-FDG-PET/CT.

BackgroundAnorectal malignant melanomas (ARMM) are rare tumors, characterized by an early lymphatic spread and distant metastasis, resulting in an extremely poor overall survival. The objective of this study was to determine the pattern of regional lymph node metastasis (LNM) by computed tomography (CT) and 18F-FDG-PET/CT in patients undergoing abdominoperineal resection (APR) and its impact on oncologic outcome.MethodsA retrospective analysis of six consecutive patients who underwent APR due to primary ARMM was performed. Patients were staged by CT and PET/CT.ResultsFour out of six patients had preoperative LNM involvement (two patients inguinal and perirectal, one iliacal, one perirectal), with two of them presenting with distant metastases additionally. Inguinal/iliacal LNM in two patients as well as liver metastasis in one patient was seen in PET/CT and missed by CT. The three patients with initial inguinal/iliacal LNM died during the observation period (overall survival: 10 (6–18) months). The three patients without inguinal/iliacal LNM involvement are currently alive, one patient showing a slowly progressive disease since 5 years, and two patients are tumor-free since 8.5 and 1.5 years (the patients had initial perirectal LNM).ConclusionsIn ARMM, PET/CT is superior to CT in detection of LNM and distant metastasis. APR is possibly a curative approach if the PET/CT shows exclusively perirectal LNM despite locally advanced tumor growth.

Abstract 3970: Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructing colon cancer

Abstract The obstructive colorectal cancer(CRC) was reported to be 7-20% of CRC. For the patients (pts) with obstructive colorectal cancer, self-expanding metallic stents (SEMS) have been useful as a palliative treatment. Insertion of SEMS for obstructive colorectal cancer is used as a bridge to surgery approach. But suspicion have been raised about whether shear forces that act on the tumor during expansion of the stent may result in a release of cancer cells into the circulation (i.e., CTCs). This study was conducted to clarify whether insertion of colonic stents results in increased levels of viable CTCs (v-CTCs). For detecting viable CTCs(v-CTCs) of CRC, we employed a novel method, TelomeScan F35 detection system. The system was constructed with a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication. 7.5 ml of peripheral blood samples were obtained before and after stent insertion and after operation. GFP-positive and CD45-negative cells were counted as v- CTCs. This study was a single institution trial, approved by the Kure Medical Center IRB. Surgical operation was scheduled within 1 month after stenting. Between October 2013 and June 2015,10 pts aged 58-89 years (5 males and 5 females) were enrolled. The surgical operation (R0) was performed in 9 cases. CEA was reduced to &amp;lt;50% of baseline value in 6 of 9 measurable pts after resection. 6 pts had no v-CTCs before stenting. Among them, 3 pts had increasing number of 1-3 v-CTCs after stenting and 1 of them developed multiple liver metastasis 12 month after resection. While, 4 pts had v-CTCs (1-19 cells) before stenting and 3 of these 4 patients had significant increase of number of v-CTCs (1-21 cells) after stent insertion. 2 of them had 12 and 14 v-CTCs, respectively after operation, despite the normalized value of CEA. The present study suggested that endoscopic stent insertion may result in tumor cell dissemination into the peripheral circulation and may induce early distant metastasis. In conclusion, v-CTCs may become useful for prognosis assessment, especially when SEMS insertion is considered. Citation Format: Shinya Yamashita. Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructing colon cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3970.

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer.

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype.

Knockdown of TAZ modifies triple-negative breast cancer cell sensitivity to EGFR inhibitors by regulating YAP expression.

Triple-negative breast cancer (TNBC) constitutes ~10-15% of breast cancer patients and represents an aggressive subtype with poor overall prognosis. TNBC is an important clinical challenge because it does not respond well to endocrine therapy and have a higher rate of early recurrence and distant metastasis following chemotherapy. Although it has been reported that the epidermal growth factor receptor (EGFR) was overexpressed in ~80% of TNBC, anti-EGFR therapy showed limited clinical benefit according to phase II studies. In this study, we first observed that knockdown of the transcriptional coactivator with PDZ-binding domain (TAZ) gene can regulate the sensitivity of TNBC cell lines to EGFR inhibitors (EGFRI) in a cell context-depended manner. Furthermore, in certain breast cancer cell lines the YES-associated protein, paralog of TAZ (YAP) expression can be upregulated by TAZ inhibition which leads to EGFRI resistance. These results suggest a specific inhibitor to TAZ/YAP combined with anti-EGFR therapy may prove effective and provide a reason why targeting EGFR showed limited clinical benefit in TNBC treatment.

HER2-positive breast cancer, how far away from the cure?-on the current situation of anti-HER2 therapy in breast cancer treatment and survival of patients.

With the diagnosis and treatment of tumor enter into the area of precision medical, based on selected targeted molecular typing of patients with individualized diagnosis and treatment play an important role. HER gene encoded epidermal growth factor receptor 2 (HER2) leading to increased early distant metastasis of breast cancer in patients and poor prognosis. However, a number of clinical studies provided evidence-based anti-HER2 targeted therapy and confirmed the benefit of anti-HER2 targeted therapy in patient survival. In recent years, through the tireless efforts of scholars in the field of breast cancer in our country, the whole diagnosis and treatment of breast cancer has accomplished an international standard. But based on a variety of factors, the anti-HER2 targeted therapy between China and the developed countries, and between different areas in China still exists certain gaps, is now a problem need to be solved. This article will analyzing the diagnostic and treatment on HER2-positive breast cancer in the United States and China, exploring reasons and looking for answers to narrow down the gap in the treatment of HER2-positive breast cancer between China and the United States. Improve the anti-HER2 targeted therapy in our country, let the patients get maximum benefit from anti-HER2 targeted therapy.

High Ki-67 and Vascular Endothelial Growth Factor (VEGF) Protein Expression as Negative Predictive Factor for Combined Neoadjuvant Chemotherapy in Young Age Stage III Breast Cancer

Background: Breast cancer was, in general, a heterogeneous disease with diverse biological characteristics, types, subtypes and clinical behavior. Its treatment and management need to be personalized and individualized. Breast cancer in young ages, although rare, is usually a unique and more aggressive cancer associated with poorer prognosis. The combination of young age and advanced stages of breast cancer would make this particular breast cancer harder to treat and cure. Unfortunately, majority of Breast Cancer Patients in Bali were in younger ages, and at advanced stages, that the mainstay of treatment was neo adjuvant chemotherapy followed by other treatment modalities. Improve prognosis only, those patients who had had a complete pathological response involving primary tumor and regional lymph nodes in the axilla. Several factors had been studied and contributed to breast cancer response to combined neo-adjuvant chemotherapy. Usually, younger patients, was associated with high proliferation rate represented by Ki-67 and early distant metastasis represented by VEGF, which also had role as prognostic markers. The purpose of this study was to determine whether high Ki-67 and VEGF expression correlate with response to NAC and hence, they would be important predictive factors for response to NAC. Method: This study was a cross-sectional and a nested case-control study of stage III breast cancers affecting patients 40 years of age or less, at Sanglah General Hospital and Prima Medika Hospital, conducted from September 1st, 2012 until March 31st, 2014. Clinical and pathology reports were traced and recorded from both hospitals; routine Immunohistochemistry (IHC) examinations were performed by both pathology labs. Statistical analysis was performed using Chi-Square test, Odds Ratio (OR), and logistic regression analysis with p<0.05. Results: There were 66 Stage III young breast cancer patients, where 35 (53%) showed no or negative response and 31 (47%) showed a positive response. Cross-sectional analysis showed that there was a significant correlation between positive Ki-67 protein expression and response to NAC (p<0.05; OR 5.538; 1.856 – 16.524; 95% C.I.) and between positive VEGF protein expression and response to NAC (p<0.05; OR. 3.455; 1.251-9.539; 95% C.I.). In Case-Control study, bivariate analysis from 62 samples had shown that higher Ki-67 expression in the study group compared to control group (p=0.004; OR. 4.747; 1.575-14.312; 95% C.I.). Bivariate analysis also showed that VEGF expression was also higher in the study group compared to control group (p=0.042; OR.2.879; 1.026-8.074; 95% CI.). Multivariate analysis had shown that an adjusted OR. 4.747 (1.575-14.312; 95% C.I.; p=0.006) for Ki-67, and an adjusted OR. 2.553 (0.860-7.582; 95% C.I.; p=0.091) for VEGF. Conclusion: We concluded that high Ki-67 and VEGF protein expression was associated with less response to combined neo-adjuvant chemotherapy/NAC and that high Ki-67 protein expression was an independent risk factor for poorer response to NAC in Stage III young age breast cancer. The possible role of high VEGF expression as a risk factor for less responsive breast cancer in younger patients had to be considered.

Analysis of early distant metastases of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer.

e15149Background: Despite standard preoperative pelvic chemoradiation (CRT) and optimal surgery with total mesorectal excision (TME) leading to local recurrence rates below 5% in locally advanced r...

Primary malignant melanoma of aryepiglottic fold

Background: Primary malignant melanoma rarely arises from noncutaneous tissues that contain melanocytes. Head and neck mucosal melanomas account for 0.7% to 3.8% of all melanomas. Here we report a case of primary malignant melanoma of aryepiglottic fold.Result: Here we reported a case of primary malignant melanoma of aryepiglottic fold.Conclusion: Primary aryepiglottic fold melanoma is an exceptionally rare neoplasm with early distant metastases and aggressive fatal course. Early diagnosis and proper line of treatment are crucial for survival. Physicians should keep a high index of suspicion for diagnosis of this rare tumor especially in old age with pigmented or non-pigmented lesion in larynx.

LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway

Pancreatic cancer (PC) remains one of the most lethal malignant tumors; early distant metastasis commonly results in poor prognosis. Recent studies confirmed the pivotal role of the long non-coding RNAs (lncRNAs) in tumorigenesis and metastasis of malignant tumors, including PC. However, little is known about the role of LincRNA-ROR (linc-ROR) in PC. In the present study, we found that linc-ROR was upregulated in PC tissues. Overexpression of linc-ROR promoted cells proliferation, migration, invasion and metastasis both in vitro and in a mouse model. Contrarily, knockdown of linc-ROR attenuated proliferation, invasion and distant metastasis. Mechanistically, we confirmed that linc-ROR up-regulates ZEB1 and then induces epithelial-mesenchymal transition (EMT), which promotes the aggressive biological behaviors of PC. Together, these results indicate that linc-ROR acts as an important regulator of ZEB1, can promote invasion and metastasis in PC, and may represent a novel therapeutic target.

Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial-mesenchymal transition in melanoma cells.

Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metastatic melanoma tissues than in normal skin, cutaneous squamous cell carcinoma or basal cell carcinoma. Melanoma cells overexpressing UBE3C frequently exhibited a mesenchymal phenotype, including reduced expression of the epithelial marker E-cadherin and expression of the mesenchymal marker vimentin. Knockdown of UBE3C expression in melanoma cells significantly suppressed melanoma growth and progression. Furthermore, silencing UBE3C led to increased E-cadherin expression and decreased vimentin and Snail1 expression. Thus UBE3C promotes melanoma progression, possibly by inducing epithelial-mesenchymal transition in melanoma cells. Inhibiting UBE3C activity may suppress melanoma invasion and metastasis and may represent a targeted therapeutic approach.

Pathological features of clinical T1b renal cell carcinoma

Objective To investigate the pathological characters of clinical T1b (4<diameter≤7 cm) renal cell carcinoma and provide reference basis for the nephron sparing surgery (NSS). Methods From January 2002 to December 2014, the pathological features of clinical T1b renal cell carcinoma were studied in 710 cases, including 505 male cases and 205 female cases. The mean age was 58 years old, ranged from 26 to 88 years old. The location of tumor included 377 in left side and 383 in right side. In the recorded 372 cases, the accurate site of tumor included 137 in upper portion, 96 in middle portion and 139 in lower portion. The initial symptom included hematuria in 103 cases, back pain in 62 cases, hematuria accompanied with back pain in 34 cases and asymptom in 511 cases. The diameter of tumor ranged from 4.0 to 7.0 cm, mean 5.4 cm. We analyzed pathological features, Fuhrman grades, histologic subtype, tumor metastasis, perirenal fat invasion and vein tumor thrombosis in all patients. Results The proportions of the clear cell, papillary, chromophobe, unclassified and mixed cell histologic subtype were 75.8% (538/710), 5.1% (36/710), 4.6% (33/710), 1.1% (8/710) and 13.4% (95/710), respectively. The proportions of hemorrhage, necrosis, cystic degeneration and fibrosis were 51.0% (362/710), 30.1% (214/710), 35.4% (251/710) and 7.8% (55/710), respectively. The rates of perirenal fat invasion and vein tumor thrombosis were 4.1% (29/710) and 3.1% (22/710). Among the 710 clinical T1b renal cell carcinoma, 144 (20.3%) were Fuhrman gradeⅠ, 513 (72.3%) were grade Ⅱ, 43 (6.1%) were grade Ⅲ, 10 (1.4%) were grade Ⅳ. In 657 cases with low Fuhrman grade(Ⅰ/Ⅱ), 17 cases were noticed perirenal fat invasion.In 53 cases with high Fuhrman grade (Ⅲ/Ⅳ), 10 cases were noticed perirenal fat invasion. The analysis showed that high Fuhrman grading was concerned with the perirenal fat invasion. Conclusions Clinical T1b renal cell carcinoma has obvious heterogeneity in its biological behavior. Most of them has characters of high differentiation, low malignant tendency and good biological behavior. Rare carcinoma exhibits the aggressive character or early distant metastasis. During the nephron sparing surgery, perirenal fat should be removed and perform pathological examination. Vein tumor thrombosis should be bolt out and radical nephrectomy is recommended at the same time. Key words: Carcinoma, renal cell; Pathology; Nephron sparing surgery

Small-cell neuroendocrine carcinoma cervix: A case report of an aggressive tumor

Neuroendocrine tumors comprise a broad family of tumors that arise from the diffuse neuroendocrine cell system. Small-cell neuroendocrine carcinoma cervix is a rare tumor, accounting for up to 2% of cervical carcinomas. These are highly aggressive tumors, characterized by early distant metastasis and worse prognosis compared to other histological types occurring in the cervix. Distant sites of recurrence including lung and bone are more common (28%) than local failure (13%). We report a case of a 60-year-old woman whose disease progressed during treatment with an eventual fatal outcome.

Prognostic factors in neuroendocrine cervical carcinoma.

ObjectiveTo evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC).MethodsThe records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses.ResultsOf the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size ≥2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence.ConclusionTumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed.

Integration of photothermal therapy and synergistic chemotherapy by a porphyrin self-assembled micelle confers chemosensitivity in triple-negative breast cancer

Triple-negative breast cancer is a malignant cancer type with a high risk of early recurrence and distant metastasis. Unlike other breast cancers, triple-negative breast cancer is lack of targetable receptors and, therefore, patients largely receive systemic chemotherapy. However, inevitable adverse effects and acquired drug resistance severely constrain the therapeutic outcome. Here we tailor-designed a porphyrin-based micelle that was self-assembled from a hybrid amphiphilic polymer comprising polyethylene glycol, poly (d, l-lactide-co-glycolide) and porphyrin. The bilayer micelles can be simultaneously loaded with two chemotherapeutic drugs with synergistic cytotoxicity and distinct physiochemical properties, forming a uniform and spherical nanostructure. The drug-loaded micelles showed a tendency to accumulate in the tumor and can be internalized by tumor cells for drug release in acidic organelles. Under near-infrared laser irradiation, high density of self-quenched porphyrins in the hydrophobic layer absorbed light efficiently and converted into an excited state, leading to the release of sufficient heat for photothermal therapy. The integration of localized photothermal effect and synergistic chemotherapy conferred great chemosensitivity to cancer cells and achieved tumor regression using about 1/10 of traditional drug dosage. As a result, chemotherapy-associated adverse effects were successfully avoided. Our present study established a novel porphyrin-based nanoplatform with photothermal activity and expanded drug loading capacity, providing new opportunities for challenging conventional chemotherapy and fighting against stubborn triple-negative breast cancer.

Expression and Clinical Pathological Significance of miR-200a in Concurrent Cholangiocarcinoma Associated with Hepatolithiasis.

BackgroundApproximately 2–10% of the patients with hepatolithiasis may develop cholangiocarcinoma (CCA). Despite recent advances in the treatment of cancers, the 5-year survival rate for CCA patients currently remains poor, primarily due to early local invasion and distant metastasis of the cancer. This study aimed to investigate miR-200a expression in combined hepatolithiasis and CCA as well as its correlation with the clinical features of CCA.Material/MethodsmiR-200a expression in combined hepatolithiasis and CCA was detected by real-time reverse transcription PCR (qRT-PCR). Its correlation with the clinicopathology of CCA was analyzed by t-tests. The effect of miR-200a on the proliferation CCA cells was determined by MTT assay. The effect of miR-200a on the invasive ability of CCA cells was assessed by Boyden chamber test.ResultsThe expression level of MiR-200a in patients with combined hepatolithiasis and CCA was significantly decreased compared with patients with only hepatolithiasis (P<0.01). Furthermore, miR-200a expression in hepatic duct cancer RBE cells was substantially reduced compared with hepatolithiasis group (P<0.01). Correlation analysis showed that abnormal expression of miR-200a was only associated with the differentiation degree and metastasis of CCA. MiR-200a transfection significantly inhibited the proliferation and invasion of REB cells (P<0.01).ConclusionsMiR-200a may suppress the proliferative and invasive ability of REB cells. The reduced miR-200a expression might be correlated with the development and progression of CCA.

Use of Cytokeratin-19 Concentration to Assess Early Recurrence and Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma following Radical Resection in Patients with a Low Serum Alpha-Fetoprotein Concentration.

Cytokeratin 19 (CK-19) is a prognostic indicator of recurrence and metastasis of hepatocellular carcinoma (HCC) following radical resection. To investigate the role of CK-19 in assessment of early recurrence and prognosis in patients with hepatitis B virus (HBV)-related HCC following radical resection. In total, 235 patients with HBV-related HCC (age, 15–82 years; mean age, 54 ± 10 years) undergoing radical resection were screened for inclusion from January 2005 to December 2010. Malignant tissues and adjacent non-malignant tissues were sampled during surgery, and CK-19 and Ki-67 expression was determined by tissue microarray and immunohistochemistry. CK-19 mRNA levels in 30 randomly selected frozen HCC specimens were examined by reverse transcription polymerase chain reaction from January 2011 to June 2011. Correlations of CK-19 and Ki-67 expression with tumor recurrence, metastasis, disease-free survival (DFS), and overall survival (OS) were analyzed. Elevated CK-19 expression was correlated with early recurrence (P = 0.001), shorter DFS (P = 0.001), and reduced OS (P = 0.010). CK-19 expression was correlated with the Ki-67 index (P = 0.037), histological differentiation (P = 0.016), focal number (P = 0.044), and blood vessel tumor embolism (P = 0.002). Patients with metastasis within 1 year exhibited stronger CK-19 expression than did patients without metastasis (P < 0.05). Furthermore, early recurrence was associated with elevated CK-19 mRNA levels (χ2 = 5.761, P = 0.016).When confirmed by a low alpha-fetoprotein concentration (<400 μg/L), CK-19 expression in surgical biopsy specimens taken from patients with HCC during radical resection is an additional valuable indicator of early recurrence, distant metastasis, and poor prognosis in HBV-positive patients.

Comparison of invasive micropapillary and triple negative invasive ductal carcinoma of the breast

BackgroundInvasive micropapillary carcinoma (IMPC) of the breast and triple negative breast cancer (TNBC) are both aggressive subtypes, but little information is available on their comparison. Patients and methodsRetrospective analysis of 95 IMPC and 200 TNBC-IDC (invasive ductal carcinoma) was conducted to compare the clinicopathologic characteristics and survivals. ResultsFor IMPC, pN was the independent prognostic factor of local-regional recurrence free survival (LRRFS) (P = 0.045) and metastasis free survival (MFS) (P = 0.048), but not of overall survival (OS) (P = 0.165). For TNBC, pT and lymphovascular invasion (LVI) were both independent prognostic factors of MFS (pT: P = 0.006, LVI: P = 0.010) and OS (pT: P = 0.006, LVI: P = 0.001), but not for LRRFS (pT: P = 0.060, LVI: P = 0.503). IMPC exhibited more aggressive features than TNBC, including larger tumor size, a greater proportion of nodal involvement, and an increased incidence of LVI. After a median follow-up duration of 61 months, 5y-LRRFS rate was lower in IMPC than in TNBC, in entire cohort (71.4 ± 4.8% vs. 89.8 ± 2.2%, P < 0.001) and in node positive cases (64.2 ± 5.9% vs. 81.7 ± 4.4%, P = 0.048). A tendency of lower 5y-MFS rate was observed in TNBC compared with in IMPC, in node positive cases (63.8 ± 5.5% vs. 74.8 ± 5.5%, P = 0.053) and in node negative cases (80.1 ± 3.6% vs. 96.2 ± 3.8%, P = 0.052), but it did not reach significance. 5y-OS was similar between IMPC and TNBC (81.9 ± 4.7% vs. 79.8 ± 3.1%, P = 0.475). ConclusionsIMPC is featured with high rate of lymph node involvement which is strongly associated with high rate of LRR. TNBC is featured with high rate of early distant metastasis without increase of nodal metastases. The survival is still relatively poor even in node negative cases.

PTU-128 Novel insights into metastatic spread of oesophageal adenocarcinoma from whole genome sequencing data

Introduction The evolution of metastatic oesophageal adenocarcinoma (OAC) is poorly understood. Whole genome sequencing (WGS) across multiple metastatic sites provides the unique opportunity to study clonal evolution of OAC. Method 2 cases of junctional OAC were extensively sampled at autopsy within 4 h of death. At presentation case 1 was palliative, case 2 had potentially curative disease but progressed during treatment. 20 fresh frozen tumour samples from primary tumour and multiple metastases (adrenal, liver, pancreas, station 102, left gastric and para-aortic lymph nodes) underwent WGS. Clonal analysis involved estimating copy number status and tumour purity, followed by point mutation clustering based on allele frequency (proportion of tumour cells harbouring a mutation); clusters were referred to as clones and were annotated with driver events of clonal progression (single nucleotide variants (SNVs) and copy number events). Results 11 clones spanned all samples in case 1 compared to 5 in case 2. Median SNVs per clone were 5885 in case 1 (range 1091–29883) and 2149 (range 424–27031) in case 2. The founding clone in both cases contained the bulk of the SNVs and key potential drivers of carcinogenesis (case 1:KRAS and GATA4 amplification, case 2:TP53 mutation). Metastases in case 1 had a branching pattern of evolution; 6 clones were unique to individual metastases and only 1 was shared across sites. Clones were on average 9363 (+/-5827) SNVs distant from the founder clone demonstrating continuing evolution in metastases. Para-aortic nodal metastasis preceded local lymph node metastasis. In contrast case 2 demonstrated linear evolution with just 2 metastatic clones that were on average 1286 (+/-1219) SNVs distinct from the primary tumour; 1 was only in the adrenal, the second was shared across multiple sites suggestive of an embolic pattern of tumour seeding. The liver metastasis was identical to the primary founder clone demonstrating that metastasis to the liver was the initial event, even prior to local lymph node metastasis. Conclusion Metastases can result from contrasting patterns of clonal evolution. Both cases demonstrate the striking phenomenon of early distant metastases, prior to the development of local lymph node metastases thus challenging our traditional algorithms of tumour staging and prognostication. Additional cases are being analysed to support our findings. Disclosure of interest None Declared.