腮腺肿瘤患者行游离保留SMAS术后的复发及预后影响因素分析

摘要 目的：探讨腮腺肿瘤患者行游离保留SMAS术后的复发及预后影响因素分析。方法：以我院2016年3月-2022年1月收治的60例腮腺肿瘤患者作为研究对象。所有患者均行游离保留SMAS联合全腮腺切除术治疗。术后进行随访。采用χ²检验和独立样本t检验进行腮腺肿瘤患者预后复发及预后存活情况的亚组分析。采用Pearson检验进行相关性分析;采用Cox回归模型计算腮腺肿瘤患者预后的独立危险因素。结果：复发和未复发患者性别、年龄、BMI、糖尿病病史和高血压病史无显著差异（P＞0.05）;复发和未复发患者的淋巴结转移、病理类型、TNM分期、AJCC临床分期差异显著（P<0.05）;预后死亡和预后存活患者性别、年龄、BMI、糖尿病病史和高血压病史无显著差异（P＞0.05）;预后死亡和预后存活患者的淋巴结转移、病理类型、TNM分期、AJCC临床分期和复发情况差异显著（P<0.05）;淋巴结转移、病理类型、TNM分期、复发、AJCC临床分期与腮腺肿瘤患者预后存活情况密切相关（P<0.05）;多因素Cox分析结果显示,淋巴结转移、病理类型、TNM分期、复发、AJCC临床分期是独立危险因素（P<0.05）。结论：疾病相关因素是导致腮腺恶性肿瘤患者复发和死亡的重要因素,临床早期可针对性调整治疗方案以降低患者术后复发和恶性肿瘤。     

DNA cytometric analysis of surgically treated squamous cell cancer of the uterine cervix, stage pT1b1-pT2b

OBJECTIVE: To determine the utility of DNA content and DNA-related variables of proliferative activity regarding prognosis in cervical cancer. STUDY DESIGN: DNA image (ICM) andflow cytometry (FCM) were performed to determine the DNA index (DI), 5c-exceeding rate (5c-ER), S-phase fraction (SPF) and proliferation index (PI) in 163 patients with surgically staged pT1b1-pT2b squamous cell cancer of the uterine cervix and treated with primary radical hysterectomy. ICM was performed on imprint cytology, obtained from fresh tumor tissue, which was also used for FCM. Results were analyzed using the chi2 test and Cox regression analysis for risk of pelvic lymph node involvement, tumor recurrence and recurrence-free survival (RFS). RESULTS: ICM was performed on all 163 and FCM on 133 samples. One-third of the tumors showed DNA aneuploidy. Analysis demonstrated prognostic significance of a DI > or = 1.70, with a (70:30) 2.3-fold risk of recurrence (P=.024) and reduced RFS of 10 months (P=.003) in cases of DI > or = 1.70. A high 5c-ER > 11% was associated with pelvic lymph node involvement and decreased RFS (P < or = .04). Significantly more relapses were found in tumors with SPF > 12% (70.8% vs. 29.2%, P=.007). RFS was markedly reduced in tumors with high SPF (52.3 vs. 61.1 months, P=.011). Low proliferative tumors (PI<25%) were associated with lower stage (P=.036) and increased RFS (61.2 vs. 47.1 months, P=.028). In multivariate analysis of clinicopathologic variables (pT category, nodal status, lymphovascular space involvement) and DNA related variables, pelvic lymph node involvement was the only significant predictor of RFS. In patients with nodal involvement, tumors with DI >1.70 were associated with lessfavorable outcomes. CONCLUSION: DNA-related variables of cell cycle analysis were valuablefor predicting prognosis in cervical cancer patients. Tumors with DI>1.70, 5c-ER >11% and high proliferative activity (SPF>12%, PI>25%) represent a subgroup with a poor prognosis.     

DNA ploidy and survival in breast cancer patients

Flow cytometric DNA ploidy measurements using frozen or deparaffinized tumor specimens were performed on 565 primary breast cancers from patients treated in the period 1975-1984. Twenty-nine percent of the cases were diploid, 61% had a single aneuploid stemline, and 10% were multiploid. Aneuploid tumors more often had negative estrogen receptor values than diploid tumors, but no significant correlation was found between ploidy class and TNM stage. Patients with more than ten positive axillary lymph nodes had predominantly aneuploid tumors. Overall and distant relapse-free survival were higher for patients with diploid tumors and low-aneuploid tumors. Stratification of the patients according to degree of lymph node involvement, TNM stage, and menopausal stage showed that the prognostic effect of aneuploidy was apparent predominantly in patients with locally advanced disease. Postmenopausal node-positive patients with diploid tumors had a significantly better prognosis than those with aneuploid tumors, but this difference was not found for the comparable premenopausal group. Multivariate analysis with the Cox proportional hazards model indicated that ploidy is an additional, independent prognostic factor in postmenopausal patients.     

Application of DNA flow cytometry to paraffin-embedded archival material for the study of aneuploidy and its clinical significance

By using a recently developed flow cytometric method we have analyzed cellular DNA content of paraffin-embedded histological material from cancer patients. This method allows the retrospective study of tumors from patients whose clinical outcome is already known, and we have applied it to ovarian cancers, stage II breast cancers, and to metastatic adenocarcinoma of unknown primary site. In addition to knowledge of patient survival, comprehensive information was available about other prognostic determinants and treatment received, and we have used multivariate analysis in an attempt to determine the prognostic significance of cellular DNA content. In ovarian cancer, it is a major prognostic variable except in stage IV disease, whereas in metastatic adenocarcinoma of unknown primary site cellular DNA content has no influence on survival. For stage II breast cancer the situation is more complex and requires larger numbers to be studied. However, aneuploid tumors tend to have more extensive involvement of axillary lymph nodes and a poorer overall disease-free survival. This influence of DNA content on disease-free survival appears to be confined to premenopausal patients, and has no effect on patient survival following disease recurrence. Although we need to study more patients and more tumor types, taken together the results so far show a generally more favorable prognosis for patients with diploid tumors, except in the presence of recurrent or metastatic disease. The better prognosis associated with diploid tumors could be due to the fact that they are more commonly found in earlier clinical stages rather than to their being inherently less aggressive than aneuploid tumors.     

Expression of enzymes and oncogene induced after radiotherapy and/or chemotherapy in patients with brain tumors.

The relationship between the degree of the expression of Cu/Zn SOD, GST-pi and bcl-2 in the initial and recurrent tumor tissue after radiotherapy and/or chemotherapy and the cellular heterogeneity obtained from DNA content by image cytometry was investigated. Subjects were 7 patients who had glial tumors which were surgically removed at onset and removed a second time at recurrence. Radiotherapy and chemotherapy were also administered after initial resection. Immunoreactivity for copper/zinc super oxide dismutase (Cu/Zn SOD), GST (glutathione-S-transferase)-pi, and bcl-2 were evaluated from routinely prepared tissue blocks. Tumors were classified into two groups by cytometric analysis of DNA ploidy in the G2M cell cycle phase. One tumor group consisted of single clonal cells in both the initial and recurrent tumors and the other group consisted of tumors with polyclonal cells in the initial and recurrent tumor. In this study, one patient (case 3) with single clonal cell glioblastoma at recurrence did not show high Cu/Zn SOD activity after radiotherapy and chemotherapy but showed a short survival time after recurrence. In three patients (cases 1, 2, 3) with single clonal-cell glioblastoma, the recurrent tumor cells showed high GST-pi immunoreactivity and survival time was short after recurrence. Tumor cells in two patients (cases 5, 7) with single clonal cell anaplastic glioma at recurrence, showed high GST-pi immunoreactivity and had a short survival time after recurrence. In three single clonal glioblastomas (cases 1, 2, 3), the recurrent tumor showed the increased bcl-2 immunoreactivity and showed a short survival time after recurrence. In two patients (case 5, 7) with single clonal cell anaplastic glioma at recurrence, tumor cells showed a high bcl-2 immunoreactivity and these patients showed a short survival time after recurrence. Although the number of subjects is very small, our study shows that the immunoreactivity of bcl-2 and GST-pi in malignant gliomas may be very important factors in radio- and chemosensitivity, and shows that GST-pi is induced by radiation and anti-cancer drugs.     

High-frequency microsatellite instability and BRAF mutation (V600E) in unselected Serbian patients with colorectal cancer

Microsatellite instability (MSI) is a genetic consequence of a MisMatch Repair defect in colorectal cancer (CRC). We compared clinicopathohistological features with MSI status of CRC and evaluated prognostic significance of MSI status and BRAF mutation in the group of MSI-H tumors. 155 primary CRCs were excised surgically, 2006–2008. MSI analysis was carried out using a fluorescence-based pentaplex polymerase chain reaction technique. BRAF mutation (V600E) was analyzed by direct sequencing in MSI-H tumors. For all patients were evaluated: age, gender, localization, tumor cell type, tumor differentiation, mucin production, lymphocytic infiltration (TILs) and TNM stage. Patients’ disease-free survival (DFS) was compared according to MSI and BRAF status using Kaplan–Meier test. Of the 155 CRCs, 19 (12.3%) were MSI-H, and 136 (87.7%) were MSS/L. BRAF mutations were found in 4 of the MSI-H tumors. Patients with MSI-H CRC had lower recurrence rate (log rank test; P = 0.04) than MSS/L group. Patients with MSI-H tumor and BRAF mutation had worse DFS than MSI-H tumors without this mutation (log rank test; P = 0.01). Most of the clinicopathologic characteristics of MSI-H CRC in Serbian patients are similar to those reported in previous studies. Patients with MSI tumor phenotype had favourable prognosis, but in those with BRAF mutation higher recurrence rate was observed.     

Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-ErbB2, c-myc and EGFr as prognostic factors in gastric cancer

Gastric cancer (GC) continues to be a highly aggressive malignancy with poor prognosis and low survival rates. The survival of patients with GC depends mainly on the stage of the disease, with early GC having a 5 year survival of 90-100% and advanced tumors a 5 year survival of 15-25%. The role of other prognostic factors in these tumors is still under investigation. 28 gastric dysplasia, 45 Early GC and 98 Advanced Gastric Cancers were evaluated for expression of the oncogenes p53, c-ErbB2, c-myc and the EGFr in paraffin-embedded material utilizing Avidin-Biotin immunohistochemistry techniques. In 34 cases of GC microvessel density (MVD) was determined in CD34 stained sections. Statistical correlations with stage, histologic type, differentiation degree, location, size, ploidy patterns and overall survival were done. The Mantel-Cox test was performed to evaluate which factors had an independent prognostic value. Both, tumor angiogenesis and p53 protein expression were statistically associated (95% confidence intervals) with overall survival in patients with GC. p53 protein expression was also correlated with cardial location, nodal involvement and tumor stage. c-ErbB2 may recognize a group of highly aggressive well differentiated adenocarcinomas with worse prognosis. c-myc was also significantly enhanced in well differentiated tumors. EGFr showed no significant associations. Mantel-Cox was performed to compare the prognostic value of tumor stage, p53 protein expression and tumor angiogenesis. Tumor angiogenesis was the most important prognostic indicator to predict overall survival in our series. p53 expression was not independent and did not provide additional prognostic information to tumor stage. Our study suggests that angiogenesis as demonstrated by microvessel counts in CD34 stained sections is a significantly important prognostic factor for predicting survival in gastric cancer.     

肿瘤淋巴管入侵与无淋巴结转移膀胱癌复发及预后的相关性分析

目的:分析肿瘤淋巴管入侵与无淋巴结转移膀胱癌复发和预后之间的关系。方法:选取临床资料完整的膀胱癌病例72例,分为淋巴结转移组(32例)和无淋巴结转移组(40例)。采用Spearman相关分析探讨淋巴管入侵与膀胱癌复发和预后的相关性,应用Kaplan-Meier法描绘生存曲线,Cox比例危险度模型筛选影响膀胱癌患者预后的因素。结果:在72例膀胱癌组织中,淋巴管入侵的阳性率是48.6%(35/72),淋巴管入侵的阳性率随肿瘤分期和分级增加而显著升高(P0.05);淋巴结转移组的淋巴管入侵阳性率为68.8%(22/32),显著高于无淋巴结转移的32.5%(13/40)。淋巴管入侵与膀胱癌的临床分期、分级、淋巴结转移以及无淋巴结转移膀胱癌复发均显著相关(P0.05)。淋巴管入侵阴性的患者的五年总体生存率显著高于淋巴管入侵阳性者,淋巴管入侵是无淋巴结转移膀胱癌复发和预后不良的危险因素。结论:肿瘤淋巴管入侵与膀胱癌临床分期和淋巴结转移密切相关,并影响膀胱癌患者的总体生存率,可作为无淋巴结转移膀胱癌复发和预后的预测因素。     

Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers

Purpose

Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC) to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results.

Patients and Methods

Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB), residual disease in breast and nodes (RDBN), tumor response ratio, Sataloff’s classification, and Miller—Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival.

Results

In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN) had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan—Meier curves.

Conclusion

Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR+/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC.     

Unilateral multicentric breast cancer

Clinical characteristics of unilateral multicentric breast cancer (UMBC) were explored depending on aggressiveness, survival rate, disease-free period and local recurrence. The study included 296 women with breast cancer, surgically treated between 1990 and 2001. UMBC was histologically proved in 29 (9.8%) patients. Multicentricity was defined by following criteria: a) tumor with minimum one satellite node in the same or other quadrant of the breast; b) minimum one cut through the breast without tumor cells; c) histopathologically, discontinued tumors with intra-ductal invasion. The average age of patients was 63.4 (range 36-85). There were 9 (31.0%) women with one satellite node, 7 (24.1%) women with two satellite nodes, and 13 (44.8%) women with three or more satellite nodes. At the operation, axilla was positive in 20 (68.9%) women. Steroid receptors were highly positive in 12 (41.4%) patients. Primary and secondary tumors were of the same histological type in 26 (89.6%) patients. Local recurrence was found in only 3 (10.3%) patients. A five-year period without disease was achieved in 24 (82.7%) women. Kaplan-Meier analysis showed a significantly higher survival rate at lower tumor stages (I or II) unlike in advanced stages with predominantly N2 grade. The results of this study showed a slightly lower five-year disease-free period than in the case of patients with monocentric breast cancer (MOBC). The survival rate was significantly lower at all advanced stages, especially determined by N2 axilla. Therefore, the conclusion is that multicentricity doesn't increase the risk of poor prognosis, especially at lower tumor stages.     

A Long-Term Follow-Up and Comprehensive Observation of Risk and Prognosis Factors of Recurrence and Survival After Resection of Hepatocellular Carcinoma

Although HBV, liver function and tumor characteristics were proven as hepatocellular carcinoma (HCC) prognosis-related, no large-scale and long-term follow-up studies have ever given robust evidence about prognosis predictive effect and contribution to different stage of postoperation. In this study, we evaluated the influence of above index on overall survival (OS) and disease-free survival (DFS) and other clinical data in a rather large population and long-term follow-up. Our study consisted of 1,326 HCC patients who underwent radical resection from 1996 to 2010. Epidemiology, clinical and prognosis data were analyzed. Risk factors of OS and DFS were explored. Cumulative survival comparison between groups was performed with log-rank. Multivariate analysis for independent prognostic factors was determined by Cox proportional hazards model. HBsAg status was a universal factor of HCC recurrence, while preoperational albumin (ALB) and portal vein tumor thrombus (PVTT) affected survival during the whole lifetime. Early stage recurrence was associated with capsule intact [OR (95 %) = 1.54,1.12–2.12, p = 0.009], preoperational alpha-fetoprotein (AFP), TNM and BCLC stages were the most important prognosis factors of recurrence in the early 5 years and PVTT affected the rest time. Survival was mainly associated with tumor characteristic and ALB. Short-time survival was affected with age and AFP, while BCLC was related with the long-time survival. We confirmed that during different periods after resection, factors affecting prognosis did not remain unchanged. Liver function and tumor characteristic affected DFS and OS the whole time, especially the early recurrence. However, HBV infection situation was associated with later recurrence. PVTT showed an opposite effect between early and later recurrence.     

Data on the Recurrence of Breast Tumors Fit a Model in which Dormant Cells are Subject to Slow Attrition but Can Randomly Awaken to Become Malignant

We successfully modeled the recurrence of tumors in breast cancer patients, assuming that:(i) A breast cancer patient is likely to have some circulating metastatic cells, even after initial surgery. (ii) These metastatic cells are dormant. (iii) The dormant cells are subject to attrition by the body’s immune system, or by random apoptosis or senescence.(iv) Recurrence suppressor mechanisms exist. (v) When such genes are disabled by random mutations, the dormant metastatic cell is activated, and will develop to a cancer recurrence. The model was also fitted to data on the survival of pancreatic cancer patients. The time course of cancer recurrence in a group of poor prognosis breast cancer patients could not be linked to the over- (or under-) expression of any gene in the primary tumors from which the recurrent tumors derived. Thus, the recurrence of the tumor in breast cancer patients appears to be a random event. Inasmuch as the kinetics of cancer recurrence in published data sets closely follows the model found for the appearance of sporadic retinoblastoma, tumor recurrence could be triggered by mutations in awakening-suppressor mechanisms. The retinoblastoma tumor suppressor gene was identified by tracing its occurrence in familial retinoblastoma pedigrees. Will it be possible to track the postulated cancer recurrence, awakening suppressor gene(s) in early recurrence breast cancer patients?     

Prognostic value of DNA flow cytometry in sympathoadrenal paragangliomas.

OBJECTIVE: To determine whether ploidy patterns are related to prognosis in sympathoadrenal paragangliomas (SAP) using flow cytometry. STUDY DESIGN: DNA flow cytometric analysis of formalin-fixed, paraffin-embedded tumor samples from 36 patients with SAP was performed. Eight cases fulfilled at least one of the following malignancy criteria: (1) extensive invasion of adjacent structures (5 cases), (2) local recurrence (3 cases), or (3) metastases (4 cases). RESULTS: Of the 36 tumors, 22 (61%) showed nondiploid patterns (12 aneuploid, 10 tetraploid). All diploid tumors were benign, while all malignant cases showed nondiploid patterns (P = .0131). The differences between diploid and aneuploid tumors and between diploid and tetraploid tumors, with regard to the malignancy of the disease, were statistically significant (P = .03311 and .01976, respectively). Only one malignant tumor had a DNA index < 1.75 (P = .00259). CONCLUSION: Anomalous DNA ploidy patterns are frequent in SAP, without necessarily implying malignancy. However, diploid DNA content may be a marker of a good prognosis. The likelihood of malignancy is greater in the tetraploid and peritetraploid range.     

Clinical prognostic factors for pediatric extra-abdominal desmoid tumor: analyses of 66 patients at a single institution

Background and purpose

Pediatric desmoid tumor (PDT) is rare and has a high local recurrence rate. The purpose of the present study was to analyze clinical risk factors of local recurrence in PDT patients.

Materials and methods

We reviewed clinical data of 66 PDT patients from 2004 to 2015. All patients underwent macroscopically complete resection, and some recurrent tumors were prescribed radiotherapy. Factors such as sex, age at presentation, location, and proximity to nerves or vasculature were analyzed. The local recurrence rate and recurrence-free survival were analyzed with these factors.

Results

All patients in the present study were children and had extra-abdominal tumors. The median follow-up time was 6.6?years. Thirty-six (55%) patients had local recurrence. Age, sex, tumor site, tumor size, and proximity to nerves/vasculature had a significant impact on prognosis in univariate analysis. Radiotherapy decreased the local recurrence rate. In multivariate analysis, younger age, tumor location in buttocks, larger tumor, and proximity to important nerves/vasculature were independent risk factors for poor prognosis.

Conclusions

Favorable therapeutic strategies could be selected according to the preoperative prognostic risk factors. Radiotherapy should be considered for local recurrence of PDT.

     

Expression of pim-1 in Tumors,Tumor Stroma and Tumor-Adjacent Mucosa Co-Determines the Prognosis of Colon Cancer Patients

Provirus integration site for Moloney murine leukemia virus (pim-1) is a proto-oncogene that is linked to the development and progression of several cancers. In this study, we evaluated pim-1 expression in tumors, tumor stroma and tumor-adjacent mucosa together as an independent prognostic factor for colon cancer patients. The study included 343 colon cancer patients. Immunohistochemical staining was used to detect pim-1. Multivariate cox regression for disease-free survival (DFS) were used to identify independent prognostic factors. Analytic hierarchy process (AHP) was used to calculate the weight of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa in order to obtain a Pim-1 total score (PTS) for recurrence and survival. Kaplan–Meier DFS curves and OS curves for patients with different pim-1 expression levels were compared using the log-rank test. In this study, four independent prognostic factors were identified for colon cancer patients: pim-1 expression in tumors, tumor stroma, tumor-adjacent mucosa, as well as tumor stage. It has been established that clinical stage is an important prognostic factor for colon cancer patients. However, PTS can identify the patients who are likely to recur not only in the whole radical excision group but also within each stage of this group. Based on the results of this study we can conclude that the PTS combined with clinical staging system may be a better predictor of colon cancer patients’ prognosis than using the clinical stage system alone. Clinical Trials Gov. Number: ChiCTR-PRCH-12002842     

Prevalence of molecular subtypes and prognosis of invasive breast cancer in north-east of Morocco: retrospective study

ABSTRACT: BACKGROUND: Breast carcinoma is known as a heterogeneous disease because gene expression analyses identify several subtypes and the molecular profiles are prognostic and predictive for patients. Our aim, in this study, is to estimate the prevalence of breast cancer subtypes and to determine the relationship between clinico-pathological characteristics, overall survival (OS) and disease free survival (DFS) for patients coming from north-east of Morocco. METHODS: We reviewed 366 cases of breast cancer diagnosed between January 2007 to June 2010 at the Department of pathology. Age, size tumor, metastatic profile, node involvement profile, OS and DFS were analyzed on 181 patients. These last parameters were estimated by Kaplan-Meier analysis and log-rank test to estimate outcome differences among subgroups. RESULTS: The average age was 45 years, our patients were diagnosed late (57% stage III, 17.5% stage IV) with a high average tumor size. Luminal A subtype was more prevalent (53.6%) associated with favorable clinic-pathological characteristics, followed by luminal B (16.4%), Her2-overexpressing (12.6%), basal-like (12.6%) and unclassified subtype (4.9%).Survival analysis showed a significant difference between subtypes. The triple negative tumors were associated with poor prognosis (49% OS, 39% DFS), whereas the luminal A were associated with a better prognosis (88% OS, 59% DFS). The luminal B and the Her2-overexpressing subtypes were associated with an intermediate prognosis (77% and 75% OS, and 41% and 38% DFS respectively). CONCLUSION: This study showed that molecular classification by immunohistochemistry was necessary for therapeutic decision and prognosis of breast carcinoma. The luminal A subtype was associated with favorable biological characteristics and a better prognosis than triple negative tumors that were associated with a poor prognosis and unfavorable clinic-pathological characteristics.     

Transketolase-like 1 expression is modulated during colorectal cancer progression and metastasis formation

Background

Transketolase-like 1 (TKTL1) induces glucose degradation through anaerobic pathways, even in presence of oxygen, favoring the malignant aerobic glycolytic phenotype characteristic of tumor cells. As TKTL1 appears to be a valid biomarker for cancer prognosis, the aim of the current study was to correlate its expression with tumor stage, probability of tumor recurrence and survival, in a series of colorectal cancer patients.

Methodolody/Principal Findings

Tumor tissues from 63 patients diagnosed with colorectal cancer at different stages of progression were analyzed for TKTL1 by immunohistochemistry. Staining was quantified by computational image analysis, and correlations between enzyme expression, local growth, lymph-node involvement and metastasis were assessed. The highest values for TKTL1 expression were detected in the group of stage III tumors, which showed significant differences from the other groups (Kruskal-Wallis test, P = 0.000008). Deeper analyses of T, N and M classifications revealed a weak correlation between local tumor growth and enzyme expression (Mann-Whitney test, P = 0.029), a significant association of the enzyme expression with lymph-node involvement (Mann-Whitney test, P = 0.0014) and a significant decrease in TKTL1 expression associated with metastasis (Mann-Whitney test, P = 0.0004).

Conclusions/Significance

To our knowledge, few studies have explored the association between variations in TKTL1 expression in the primary tumor and metastasis formation. Here we report downregulation of enzyme expression when metastasis appears, and a correlation between enzyme expression and regional lymph-node involvement in colon cancer. This finding may improve our understanding of metastasis and lead to new and more efficient therapies against cancer.     

Histologic Parameters Predictive of Disease Outcome in Women with Advanced Stage Ovarian Carcinoma Treated with Neoadjuvant Chemotherapy

The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen's kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of [20]months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.     

Does Tumor Size Improve the Accuracy of Prognostic Predictions in Node-Negative Gastric Cancer (pT1-4aN0M0 Stage)?

Background

The prognostic importance of tumor size in gastric cancer is unclear. This study investigated whether the inclusion of tumor size could improve prognostic accuracy in node-negative gastric cancer.

Methods

Clinical and pathological data of 492 patients with node-negative gastric cancer who underwent radical surgery in our department from January 1995 to December 2008 were analyzed. The prognostic accuracy of T stage was compared with that of T stage plus tumor size. The ability of tumor size to improve the 95% confidence interval (CI) of postoperative 5-year survival rate in gastric cancer patients was assessed. Different T stages plus tumor size were further analyzed to assess improvements in prognosis.

Results

Mean tumor size was 3.79±1.98 cm with a normal distribution. Multivariate analysis showed that tumor size and T stage were independent prognostic factors. Postoperative 5-year survival rate tended to decrease as tumor size increased in 1 cm increments. The addition of tumor size to T stage improved accuracy in predicting 5-year survival by 4.2% (P<0.05), as well as improving the 95% CI of postoperative 5-year survival rate by 3.2–5.1%. The addition of tumor size improved the predictive accuracy of postoperative 5-year survival rate by 3.9% (95% CI 70.4%–91.1%, P = 0.033) in patients with stage T3N0M0 tumors and by 6.5% (95% CI 68.7%–88.4%, P = 0.014) in patients with stage T4aN0M0 tumors.

Conclusions

Tumor size is an independent prognostic factor for survival in patients with node-negative gastric cancer, as well as improving prognostic accuracy in stage T3/4aN0M0 tumors.     

Prognostic significance of p53, bcl-2 and EGFR in carcinoma of the endometrium

OBJECTIVE: To evaluate the part played by several parameters in the prognosis of patients with endometrial carcinoma. STUDY DESIGN: Eighty imprint smears from fresh endometrial tumor specimens were studied immunocytochemically for the expression of p53, bcl-2 and epidermal growth factor receptor. Also, the presence of estrogen receptor (ER) and progesterone receptor (PR) in the tumor tissue was measured. The data obtained were related to survival, and associations were sought between the parameters studied. RESULTS: Strong associations were found between advanced stage, high grade, lymph node metastases at diagnosis, nonendometrioid histology and p53 expression with poor survival. Bcl-2 expression was associated with good five-year survival. ER expression was associated marginally with good five-year survival, but PR expression was not. A strong association was found between p53 and advanced disease, stage and lymph node metastases at diagnosis. An association between EGFR positivity and survival was not found. CONCLUSION: p53 Expression of uterine tumors is an independent and strong indicator of poor prognosis. Even patients with stage I and II disease at surgery who have p53-positive tumors must be considered at high risk.