Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes.

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P =.04) and a clinical response to chemotherapy > or = 50% (P =.003) were associated with negative axillary status at dissection. An initial tumor size < or = 3 cm (63 patients) was associated with pCR of the primary tumor (P =.02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P =.003), absence of residual nodal disease (P =.01), and pCR of the tumor (P =.05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% +/- 14.9% among patients with no involved nodes at the time of surgery and 48.7% +/- 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age < or = 40 years (P =.002), persistence of nodal involvement (P =.03), and S-phase fraction greater than 4% (P =.02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.     

TS、p53基因产物表达水平与直肠癌预后的关系

目的：探讨TS基因和p53基因产物表达与直肠癌术后复发转移和预后的关系。方法：采用免疫组织化学方法对42例直肠癌手术标本中的TS基因和p53基因产物进行检测和分析：结果：TS基因产物的高表达率为45．5％(20／42)，p53基因产物的高表达率为43．2％(19／42)。TS基因产物低表达患的局部复发率和远处转移率明显低于高表达患(P=0．014，0．005)，无病生存期明显长于高表达患(P=0．0006)：在24例术后辅助化疗患中，TS基因产物低表达患的局部复发率和远处转移率均明显低于高表达患(P=0．007，0．005)：p53基因产物高表达与局部复发、远处转移以及无病生存期之间未见明显的相关性。多因素分析结果显示TS基因产物表达是影响直肠癌患术后无病生存期的独立因素。结论：TS基因产物表达与直肠癌术后的复发转移和无病生存期有关。     

Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution

BACKGROUND: The authors explored the prognostic factors and clinical outcomes of patients who had malignant peripheral nerve sheath tumors (MPNST) with and without neurofibromatosis type 1 (NF-1). METHODS: Two hundred five patients with localized MPNST who underwent surgery at the Istituto Nazionale per lo Studio e la Cura dei Tumori (Milan, Italy) over 25 years were reviewed. Forty-six patients had concomitant NF-1 syndrome, and 159 patients did not. Local recurrence, distant metastases, and survival rates were studied. RESULTS: One hundred thirty patients presented with primary disease, and 75 patients had locally recurrent tumors. The disease-specific mortality rate was 43% at 10 years, with a continuously disease-free survival rate of no greater than 40%. Presentation with either primary or recurrent disease, tumor size, and tumor site (trunk vs. extremity) were the strongest independent predictors of survival. Margin status and radiation therapy also played a role, mostly related to their effect on local outcome. Pathologic grade influenced distant metastases, but only a trend for survival could be observed. No significant independent differences between patients with and without NF-1 were observed. CONCLUSIONS: To the authors' knowledge, this was among the largest single-institution series to date. The results confirmed that patients with MPNST share similar prognostic factors with patients who have other soft tissue sarcomas and have some of the worst clinical outcomes. The presence of NF-1 syndrome per se did not affect survival, but patients with NF-1 were more likely to have larger tumors. Therefore, such patients should be followed carefully to detect disease as early as possible.     

LIMCH1 as a New Potential Metastasis Predictor in Breast Cancer

Background and objective: High LIMCH1 expression in lung and renal cancer is determined as a favorable prognostic factor. However, prognostic value of LIMCH1 expression in breast cancer has not been studied yet. Therefore, this study was performed to determine the prognostic value of LIMCH1 expression in breast cancer patients. Methods: This retrospective study included 89 patients with invasive breast carcinoma of no special type. These patients referred to  Cancer Research Institute of Tomsk National Research Medical Center from 2007 to 2018. LIMCH1 protein expression in tumor cells was detected by immunohistochemical analysis in this study. Statistical analysis was done to investigate the possible relationship between LIMCH1 protein expression and clinicopathological parameters, risk of metastasis, distant metastasis free survival, and overall survival. Results: IHC analysis of breast cancer tissue samples revealed that LIMHC1 protein expression was found in 29.2% (26/89) of the cases. Lymph node and distant metastases were more frequent in patients with LIMCH1 protein expression. LIMCH1 protein expression increased the risk of distant metastasis based on our findings. LIMCH1 protein affected metastatic-free survival regardless of the T, as well as other clinical and pathological parameters (p=0.0146, HR=3.2058 (1.26; 8.17)). Moreover, LIMCH1 protein expression was associated with worse overall survival (p=0.0071, HR=2.73 (1.28; 5.85)) in our breast cancer patients. Conclusion: LIMCH1 protein expression was associate with metastases development, providing prognostic stratification. In breast cancer, LIMCH1 protein expression was found as an unfavorable prognostic factor of distant metastasis-free survival based on our findings.     

Adult Pelvic Sarcomas: A Heterogeneous Collection of Sarcomas?

Introduction. Adult pelvic soft tissue sarcomas are a rare group of heterogeneous malignancies. These sarcomas differ from extremity and trunk soft tissue sarcomas in presentation, characteristics and response to treatment.Methods. A retrospective analysis of patient and tumor characteristics, treatment and prognosis and prognostic factors was performed.Results. Between 1977 and 1997, a total of 33 adult patients with soft tissue sarcomas involving the pelvis but excluding uterine leiomyosarcoma were identified. Leiomyosarcomas (18), including six GIST, and rhabdomyosarcomas (eight) were the most commonly seen tumors. At first presentation, nine patients already had metastases. The mean follow-up was 52 months (1-200). Recurrences developed in 15 of the 24 cases (63%) with tumors without metastases at first presentation; in six (25%) recurrence was locally only, in nine distant metastases occurred. The nine patients with metastatic disease at first presentation died of the disease, while eight of the 24 patients with localized disease at presentation died. One patient died of an unrelated cause, four were alive with disease, and 11 patients were alive and free of disease. The only identifiable prognostic factor of disease-free interval and overall survival was histological grade.Conclusion. Soft tissue sarcomas of the pelvis appear to be associated with increased rate of metastasis at the time of diagnosis and higher rates of local recurrence. In this study, multi-modality treatment for most primary tumors did not show a significant benefit in recurrence rate, DFI and OST, when compared to single modality approach. Although the number of patients in this study is small, and different types of sarcomas were studied, the only identifiable predictor for survival was low histological grade of the tumors. The differences of this heterogeneous group of pelvic sarcomas with retroperitoneal, trunk and extremity sarcomas should be taken into consideration in the management of these sarcomas.     

Up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis

BACKGROUND: CD40 and its ligand, CD154, play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely. METHODS: One hundred twenty-nine surgical specimens of nonsmall cell lung cancer were assessed immunohistochemically for CD40 and CD154 expression, and that expression was correlated with patients' clinicopathologic parameters and outcome. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. RESULTS: Immunohistochemical staining of tumor cells confirmed that 67 patients (51.9%) were positive for CD40, and 76 patients (58.9%) were positive for CD154. The survival of patients who had tumors that were negative for CD40 was significantly better than the survival of patients who had tumors that were positive for CD40 (P = .0004). Multivariate analysis using a Cox regression model indicated that CD40 expression in cancer cells is an independent, unfavorable prognostic factor (risk ratio, 1.855; P = .0403). By using an in vitro juxtacrine growth factor assay, the growth of LK2 cells (CD40-positive/CD154-negative) was accelerated by CD154-positive cancer cells, such as PC10 cells (CD40-negative/CD154-positive), by a juxtacrine mechanism. CONCLUSIONS: The current results suggested that CD40 expression in tumors is associated with a poor prognosis and that the juxtacrine interaction of CD40-CD154 among cancer cells facilitates the development of malignant potential in nonsmall cell lung cancer.     

Kallikrein-related peptidase-6 (KLK6) mRNA expression is an independent prognostic tissue biomarker of poor disease-free and overall survival in colorectal adenocarcinoma

Members of the family of tissue kallikrein and kallikrein-related peptidases possess important prognostic value in cancer. Moreover, the oncogenic role of kallikrein-related peptidase-6 (KLK6) in colorectal cancer has been well documented so far. This study investigated the prognostic value of KLK6 mRNA expression as a molecular tissue biomarker in colorectal adenocarcinoma. For this purpose, KLK6 mRNA expression was studied in 110 primary colorectal adenocarcinomas and 39 paired noncancerous colorectal specimens. A dramatic upregulation of KLK6 mRNA expression was observed in colorectal tumors. KLK6 mRNA overexpression was associated with high depth of tumor invasion, presence of distant metastases, and tumor-node-metastasis (TNM) stage of patients. Furthermore, KLK6 mRNA expression was shown to predict poor disease-free and overall survival independently of patient gender, age, tumor size, location, histological subtype, grade, venous invasion, lymphatic invasion, TNM stage, radiotherapy, and chemotherapy treatment. Moreover, Kaplan–Meier survival analysis revealed that colorectal adenocarcinoma patients with negative regional lymph nodes (N0) and those without distant metastases (M0) harboring KLK6 mRNA-positive colorectal tumors tended to relapse and die earlier than N0 and M0 patients with KLK6 mRNA-negative colorectal adenocarcinoma. Thus, KLK6 mRNA expression could be considered as an independent, unfavorable molecular prognostic biomarker in colorectal adenocarcinoma, with additional prognostic value in patients without regional or distant metastases.     

Decreased expression of CD44 in metastatic prostate cancer.

Decreased expression of CD44 is an independent prognostic marker for surgically treated prostate cancer. To investigate immunohistochemically defined CD44 expression in primary and metastatic prostate cancer, 2 groups of patients undergoing radical prostatectomy for clinically localized prostate cancer were studied. (1) pN1 group: 23 patients, finally staged pN1, of whom the radical prostatectomy specimen and the lymph nodes were investigated to establish a correlation between CD44 expression in the concurrently resected primaries and metastases; (2) pN(0) group: 23 patients with pN(0) disease matched for pT stage and Gleason sum score with the pN(1) patients. Progression rates based on serum prostate-specific antigen (PSA) levels could be determined in 42 of these 46 patients. In addition, 28 distant metastases were studied. A CD44 score of < 10% was found in 22 of the 23 lymph node metastases (96%) and in 20 of the corresponding radical prostatectomies. In the pN(0) group this was observed in only 6 out of 23 specimens. In most of the distant metastases CD44 scores were < 10%. Patients with pN0 disease and > 10% CD44-positive tumor cells had a significantly better prognosis than the other patients who were not significantly different from each other. CD44 expression is thus strongly reduced in prostate cancer metastases as well as in the corresponding primary tumors. This reduction may be used to predict the N stage clinically, provided that CD44 scores can be determined reliably on preoperative biopsy specimens.     

Prognostic factors in 227 patients with malignant fibrous histiocytoma.

Malignant fibrous histiocytoma, the major subset of soft tissue sarcomas, was examined for prognostic factors that could influence clinical management and research. Two hundred twenty-seven patients with localized disease, having surgery as the principal modality, were reviewed retrospectively to identify clinical outcomes. The mean age of the patients was 54 years. Extremities were the primary tumor site in 157 patients (62.2%). Overall survival rate was 50%, including 38 patients who died of other causes. Distant metastases were most common to the lung (90%). Local recurrence alone occurred in 37 patients (16%), distant metastases alone in 52 (23%), and distant metastases with local recurrence in 25 (11%). The primary tumor size indicated the 5-year survival rate: tumors smaller than 5 cm had a survival rate of 82%; 5 to 10 cm, 68%; and larger than 10 cm, 51%. Intermediate-grade tumors yielded a 5-year survival rate of 80%, and the 5-year survival rate for high-grade tumors was 60%. Survival rates for both grades were affected by size: tumors of high grade and smaller than 5 cm in diameter had a survival rate of 79%; 5 to 10 cm, 63%; and more than 10 cm, 41%. Grade and size emerge as significant prognostic indicators. These variables will prove helpful in treatment decisions and design of clinical studies.     

Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis

Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.     

Vascularization in primary breast carcinomas: its prognostic significance and relationship with tumor cell dissemination.

PURPOSE: The interaction between tumor cells, stroma, and endothelial cells is important for the dissemination of tumor cells. The aim of the present study is to examine vascularity in primary breast carcinomas and its prognostic significance and relationship with tumor cell dissemination. EXPERIMENTAL DESIGN: A total of 498 invasive breast carcinomas were analyzed. Representative tumor sections were stained for CD34 and CD105, and vascularity was quantified by the Chalkley method. The relationship between Chalkley counts, vascular invasion, disseminated tumor cells (DTC) in the bone marrow, other clinicopathologic variables, and clinical outcome was evaluated. RESULTS: High vascular grades determined by Chalkley counts were significantly associated with shorter distant disease-free survival and breast cancer-specific survival in all patients (P < 0.001, log-rank) and in node-negative patients not receiving adjuvant systemic therapy (P < 0.05). In multivariate analysis, both CD34 and CD105 Chalkley counts showed prognostic significance for distant disease-free survival (P = 0.014 and P = 0.026), whereas CD34 also showed prognostic significance for breast cancer-specific survival (P = 0.007). Vascular invasion and DTCs in the bone marrow showed independent prognostic significance. DTC did not discriminate survival for CD34 low Chalkley counts, whereas a very poor prognosis was observed for DTC-positive patients with high CD34 counts. In node-negative patients not receiving systemic chemotherapy, high CD34 and high CD105 counts in combination identified patients with unfavorable outcome, as opposed to all other CD34/CD105 combinations. CONCLUSIONS: Improved identification of risk groups could be obtained by adding CD34 and CD105 vascular analysis to DTC, vascular invasion, and other primary tumor factors. This may facilitate the selection of candidates for adjuvant systemic therapy.     

Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer

Cyclooxygenase-2 (Cox-2) expression can induce mammary tumorigenesis in transgenic mice, and selective Cox-2 inhibitors are both chemopreventive and chemotherapeutic in rat models of breast cancer. We analyzed the expression of Cox-2 protein by immunohistochemistry in tissue array specimens of 1576 invasive breast cancers. Moderate to strong (elevated) expression of Cox-2 protein was observed in 37.4% of the tumors, and it was associated with unfavorable distant disease-free survival (P < 0.0001). Elevated Cox-2 expression was associated with a large tumor size, a high histological grade, a negative hormone receptor status, a high proliferation rate (identified by Ki-67), high p53 expression, and the presence of HER-2 oncogene amplification (P < 0.0001 for all comparisons), along with axillary node metastases and a ductal type of histology (P = 0.0001 and P = 0.0017, respectively). Interestingly, association with the unfavorable outcome was especially apparent in the subgroups defined by estrogen receptor positivity, low p53 expression, and no HER-2 amplification (P < 0.0001 for all comparisons). These results indicate that elevated Cox-2 expression is more common in breast cancers with poor prognostic characteristics and is associated with an unfavorable outcome. The present findings support efforts to initiate clinical trials on the efficacy of Cox-2 inhibitors in adjuvant treatment of breast cancer.     

Expression of decorin, a small leucine-rich proteoglycan, as a prognostic factor in soft tissue tumors

BACKGROUND AND OBJECTIVES: Decorin is a major extracellular matrix protein which has recently become the focus of various cancer studies. However, there have so far been no reports describing the clinicopathological implications of decorin in soft tissue tumors. The aim of this study was to examine whether decorin expression is a prognostic factor in soft tissue tumors. METHODS: Decorin expression was examined in 85 samples obtained from 77 patients by real-time quantitative PCR and immunohistochemistry. RESULTS: Lower levels of decorin were expressed in liposarcoma and malignant peripheral nerve sheath tumor than in lipoma (<0.01) and neurofibroma (P < 0.05), respectively. An immunohistochemical analysis for spindle-cell sarcomas demonstrated decorin protein to be produced by myofibroblastic cells in the peripheral stromal extracellular spaces. On a Kaplan-Meier analysis, lower levels of decorin were associated with lower disease-free and overall survival rates (P < 0.05) in 31 spindle-cell sarcomas. A multivariate analysis revealed a significant correlation between a reduced decorin expression and a poor disease-free survival (P = 0.04). In all seven patients with recurrent or metastatic lesions, the decorin expression levels were lower in secondary lesions than in primary lesions. CONCLUSIONS: A reduced decorin expression was found to be a useful biomarker of aggressiveness in soft tissue tumor.     

Prognostic factors in localized soft-tissue sarcomas

The prognostic factors associated with local failure and overall survival and the effect of radiotherapy were determined in 77 patients with localized (extremity and nonextremity) operable soft-tissue sarcoma. There were 52 male and 25 female patients; median age was 50 years (range: 15-83). Histologic grade of the tumors was as follows: low-intermediate grade in 32 cases and high grade in 29 cases. The primary tumors were treated by marginal resection (20 patients), wide resection (52 patients), and radical resection (5 patients). Adjuvant radiotherapy was applied to 50 (65%) patients. The 5-year local recurrence-free survival rate was 70.6%. Treatment with adjuvant radiotherapy and development of metastases were the significant prognostic factors associated with local recurrence. Radiotherapy was more effective in patients with tumors 10 cm or larger, marginally resected, extremity located, and high grades. The overall survival rate was 64.4% at 5 years. Significant adverse prognostic factors were high grade tumors, presence of local recurrence, and development of metastases in univariate analyses. Development of metastases and old age were the only adverse prognostic factors by multivariate analysis. The best 5-year survival rate was obtained in female patients younger than 50 years (90%). The present study demonstrated the importance of adjuvant radiotherapy and development of metastases as prognostic factors for local control. Again, development of metastases and age were the most important prognostic factors in operable soft-tissue sarcomas.     

IMP3 predicts aggressive superficial urothelial carcinoma of the bladder

PURPOSE: In this study, we investigated whether an oncofetal protein, IMP3, can serve as a new biomarker to predict progression and metastasis of early-stage urothelial carcinoma of the bladder. EXPERIMENTAL DESIGN: The expression of IMP3 in 242 patients with primary superficial bladder urothelial carcinoma and metastatic urothelial carcinoma was evaluated by immunohistochemistry. Patients with primary superficial urothelial carcinoma of the bladder were further investigated by use of survival analysis. RESULTS: Twenty percent (42 of 214) of primary superficial urothelial carcinomas and 93% (26 of 28) of metastatic urothelial carcinomas expressed IMP3. Kaplan-Meier plots and log-rank tests showed that patients with IMP3-positive tumors had a much lower progression-free survival (P = 0.0002) and disease-free survival rate (P = 0.0067) than did those with IMP3-negative tumors. The 5-year progression-free and disease-free survival rates were 91% and 94% in IMP3-negative patients versus 64% and 76% in IMP3-positive patients, respectively. Sixty percent of IMP3-positive patients with superficial invasive urothelial carcinoma at initial diagnosis went on to develop metastases, whereas no metastasis was found in IMP3-negative patients (P = 0.0017). In the multivariable Cox analysis, patients with IMP3 expression in their superficial urothelial carcinomas subsequently developed invasive tumors or metastasis at a rate that was about five times greater than cases without expression of IMP3 adjusting for other well-known clinical variables (tumor stage and grade, etc.). CONCLUSIONS: Our findings indicate that IMP3 is an independent prognostic marker that can identify a group of patients with a high potential to develop progression and who might benefit from early aggressive therapy.     

Differential Tumor Expression of Inhibitor of Differentiation-1 in Prostate Cancer Patients With Extreme Clinical Phenotypes and Prognostic Implications

BackgroundIn the prostate-specific antigen era, potentially indolent prostate tumors are radically treated, causing overtreatment. Molecular prognostic factors might differentiate indolent from aggressive tumors, allowing avoidance of unnecessary treatment.Patients and MethodsFifty-two prostate cancer patients (20 organ-confined and 32 metastatic) were selected. All formalin-fixed and paraffin-embedded primary biopsies and matched metastases of 15 of them were evaluated for tumor and endothelial cell Id1 protein expression. Seventy-nine additional patients with organ-confined prostate cancer were selected for Id1 mRNA in silico analysis.ResultsAmong metastatic cancer subjects, 48% of primary tumors and 38% of metastases showed Id1 tumor cell expression, and 79% of primary tumors and 81% of metastases showed endothelial immunoreactivity. In the organ-confined group none of them showed Id1 protein tumor cell expression and 50% displayed endothelial expression. In the metastatic patients group, lower levels of Id1 protein predicted a nonsignificant longer overall survival (13 months vs. 7 months; P = .79). In the in silico analysis, however, lower levels of Id1 mRNA predicted a longer disease-free survival (61 months vs. not-reached; P = .018) and the hazard ratio for progression was 0.451 (P = .022) in favor of patients showing lower levels.ConclusionIn our cohort, it seems to be a differential epithelial expression of Id1 protein according to the prognostic features (metastatic/poor prognosis vs. organ-confined/good prognosis). In localized tumors treated with radical prostatectomy, higher Id1 mRNA expression levels might predict a higher hazard ratio for progression and a shorter disease-free survival. Further validation of these results in larger prospective series is warranted.     

Prognostic significance of CD100 expression in soft tissue sarcoma

BACKGROUND: CD100, a class IV semaphorin, promotes angiogenesis, invasive growth, proliferation, and antiapoptosis of cancer cells in vitro. The expression of CD100 in soft tissue sarcoma (STS) and its correlation with clinicopathologic factors and prognostic significance were evaluated. METHODS: Expression levels of CD100 in patients with localized STS were evaluated immunohistochemically on paraffin-embedded sections from 81 patients, including 47 men and 34 women with a median age of 54 years. Staining intensity was categorized into weaker than (level 1) or equal to that of lymphocytes with a rate of <10% stained tumor cells (level 2) or >10% stained tumor cells (level 3). Ki-67 staining was performed in parallel. RESULTS: Forty-two tumors (52%) had level 1 CD100 expression, 18 tumors (22%) had level 2 CD100 expression, and 21 tumors (26%) had level 3 CD100 expression. Tumors that had level 2 and 3 CD100 expression were correlated significantly with higher mitotic count, cellularity, ratio of necrosis, and Ki-67 labeling index (LI) compared with tumors that had level 1 CD100 expression. There was no correlation between CD100 expression and other characteristics. Among the 3 levels of CD100 expression, higher expression levels were correlated with poorer overall and disease-free survival. Multivariate analysis revealed that CD100 expression (levels 1 and 2 vs level 3) and tumor size (5 cm) were independent prognosticators for overall survival (P < .05 for both), and CD100 expression (levels 1 and 2 vs level 3) was an independent prognosticator for disease-free survival (P < .05). CONCLUSIONS: The results from this study indicated the demonstrated prognostic significance of CD100 expression in STS.     

Role of CD24 protein in predicting metastatic potential of uterine cervical squamous cell carcinoma in patients treated with radiotherapy

PURPOSE: The protein CD24 is a cell surface protein that appears to function as an adhesion molecule; its expression has been shown to correlate with prognosis in a variety of tumors. The aim of this study was to evaluate the immunoreactivity of uterine cervical squamous cell carcinoma to CD24 and determine whether CD24 is associated with clinical and pathologic parameters, including prognosis. METHODS AND MATERIALS: The expression of CD24 protein was immunohistochemically studied in 73 cases of uterine cervical squamous cell carcinoma. All patients were treated with definitive radiotherapy alone or with concurrent chemoradiotherapy. Two pathologists independently analyzed the immunostaining; they did not have knowledge of the patient outcomes and evaluated any changes according to the percentage of tumor cells stained as follows: negative, <5% reactive; and positive, >5% reactive. RESULTS: Positive staining was found in 43 cases (58.9%). The immunoreactivity did not correlate with age, International Federation of Gynecology and Obstetrics stage, lymph node metastasis, or tumor size. For patients who were CD24 negative, the total failure and distant metastasis rates were decreased about 20% compared with the rates for patients who were CD24 positive. On univariate analysis, the 5-year distant metastasis-free survival rate of CD24-negative patients was significantly greater than that of the CD24-positive patients (84.7% vs. 66.7%, respectively, p = 0.0497). The International Federation of Gynecology and Obstetrics stage and CD24 expression were significantly associated with distant metastasis-free survival on multivariate analysis. CONCLUSIONS: CD24 expression was a significant independent prognostic factor for distant metastasis-free survival in patients with uterine cervical squamous cell carcinoma. In the future, prospective determination of CD24 expression might aid clinical practice in the selection of the appropriate therapy for individual patients.     

Deleted in colon cancer protein expression in colorectal cancer metastases: a major predictor of survival in patients with unresectable metastatic disease receiving palliative fluorouracil-based chemotherapy.

PURPOSE: To determine whether deleted in colon cancer (DCC) protein expression in colorectal cancer (CRC) metastases could predict outcome to palliative fluorouracil (FU)-based chemotherapy and to assess whether it is similar to that observed in the corresponding primary tumors. PATIENTS AND METHODS: DCC protein expression was assessed immunohistochemically on archival specimens of CRC metastases from 42 patients homogeneously treated by methotrexate-modulated bolus FU alternated to 6-S-leucovorin-modulated infused FU and was retrospectively correlated with patient characteristics and clinical outcome. In a subset analysis, DCC immunoreactivity was compared between metastatic CRC and the corresponding primary tumors and regional lymph node metastases. RESULTS: Positive immunoreactivity for DCC was found in 45% of patients. Eighteen (78%) of 23 patients for whom multiple samples were available displayed a similar pattern of expression in distant metastases and primary tumors. The median survival time was 14.3 months in patients without DCC expression and 21.4 months in patients with DCC-positive tumors (log-rank test, P =.04); the 2-year survival rates were 8.5% and 42.5%, respectively. Response rates to chemotherapy were not significantly different between the two groups. By multivariate analysis, DCC protein expression maintained its prognostic value and showed to be the single best predictor of survival, with a relative risk of 2.16. CONCLUSION: Our results indicate that expression of the DCC protein in CRC metastases is similar to that observed in the corresponding primary tumors and represents a dominant predictor of survival in patients with unresectable, advanced CRC who are undergoing palliative FU-based chemotherapy.