Gastric cancer heterogeneity

Aretxabala, Xabier de; Yonemura, Yutaka; Sugiyama, Kazuo; Hirose, Nobuko; Kumaki, Takeo; Fushida, Sachio; Miwa, Kouichi; Miyazaki, Itsuo

doi:10.1002/1097-0142(19890215)63:4<791::aid-cncr2820630431>3.0.co;2-w

Cited by 39 publications

(13 citation statements)

References 23 publications

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“…It has been reported that 33-40% of primary stomach cancers are heterogeneous in terms of tumour ploidy (Sasaki et al, 1988;De Aretxabala et al, 1989). Systematic investigation of the variation of SPF within primary stomach cancer has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of DNA flow cytometry in stomach cancer: a 5-year prospective study

et al. 1999

Br J Cancer

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SummaryThe role of DNA flow cytometry in the prediction of prognosis for patients with stomach cancer remains to be defined. Thus we studied prospectively the role of DNA flow cytometry as a prognosis indicator in stomach cancer patients in a high-incidence area. Between November 1990 and December 1992, primary stomach cancer tissues were obtained from the surgical specimens from 217 patients (148 male, 69 female). DNA flow cytometric analyses of DNA ploidy and S-phase fraction were performed and the results were correlated with patient survival. The median age of the patients was 55 years (range 24-78). Aneuploid cell population was found in 114 of 217 samples (53%). Tumour S-phase fraction was obtained in 96 of 103 diploid tumours (93%) and 61 of 114 aneuploid tumours (54%). After median follow-up of 66.1 months, the patients with tumours with an S-phase fraction over 17% had significantly worse survival rates than patients with tumours with S-phase fractions of lower than 8% or 8-17% (45% vs 59% and 63% of patients surviving, P = 0.007). Tumour ploidy status did not correlate with patient survival. Multivariate analyses showed that the TNM stage remained the most important prognostic indicator. The tumour S-phase fraction was also an independent prognostic indicator (relative risk 2.300, 95% CI, 1.252-4.223). Tumour S-phase fraction obtained by DNA flow cytometry is an independent prognostic indicator for the survival of the patients with stomach cancer.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of DNA flow cytometry in stomach cancer: a 5-year prospective study

et al. 1999

Br J Cancer

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“…One study found HER2 to have far lower levels of heterogeneity than other biomarkers studied, with c-myc and cyclinD1 exhibiting heterogeneity in 83 and 100% of samples, respectively. 28 In regards to tumor type, high levels of heterogeneity is well known in gastric carcinoma, 29 and one study found rates of intratumoral heterogeneity of KRAS mutations as high as 35-47% in colorectal tumors. 30 HER2 expression is generally far more heterogeneous in gastric carcinoma than in breast tumors.…”

Section: Discussionmentioning

confidence: 99%

Evaluating tumor heterogeneity in immunohistochemistry-stained breast cancer tissue

Potts¹,

Krueger²,

Landis³

et al. 2012

Laboratory Investigation

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Quantitative clinical measurement of heterogeneity in immunohistochemistry staining would be useful in evaluating patient therapeutic response and in identifying underlying issues in histopathology laboratory quality control. A heterogeneity scoring approach (HetMap) was designed to visualize a individual patient's immunohistochemistry heterogeneity in the context of a patient population. HER2 semiquantitative analysis was combined with ecology diversity statistics to evaluate cell-level heterogeneity (consistency of protein expression within neighboring cells in a tumor nest) and tumor-level heterogeneity (differences of protein expression across a tumor as represented by a tissue section). This approach was evaluated on HER2 immunohistochemistry-stained breast cancer samples using 200 specimens across two different laboratories with three pathologists per laboratory, each outlining regions of tumor for scoring by automatic cell-based image analysis. HetMap was evaluated using three different scoring schemes: HER2 scoring according to American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines, H-score, and a new continuous HER2 score (HER2 cont ). Two definitions of heterogeneity, cell-level and tumor-level, provided useful independent measures of heterogeneity. Cases where pathologists had disagreement over reads in the area of clinical importance ( þ 1 and þ 2) had statistically significantly higher levels of tumor-level heterogeneity. Cell-level heterogeneity, reported either as an average or the maximum area of heterogeneity across a slide, had low levels of dependency on the pathologist choice of region, while tumor-level heterogeneity measurements had more dependence on the pathologist choice of regions. HetMap is a measure of heterogeneity, by which pathologists, oncologists, and drug development organizations can view cell-level and tumor-level heterogeneity for a patient for a given marker in the context of an entire patient cohort. Heterogeneity analysis can be used to identify tumors with differing degrees of heterogeneity, or to highlight slides that should be rechecked for QC issues. Tumor heterogeneity plays a significant role in disconcordant reads between pathologists.

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“…Only Yonemura et al (1990a) showed a signi®cant dierence in patient survival in relation to the Ki-67 labeling rate in an earlier study. These varying results might be due to a well-known fact: the great intratumoral heterogeneity of gastric carcinomas (De Aretxabala et al 1989). Most carcinomas consist of a heterogeneous population of tumor cells, within which there are dierent proliferation rates (Brown and Gatter 1990).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the proliferation index in gastric carcinomas with the monoclonal antibody MIB 1

Broll¹,

Mahlke²,

Best³

et al. 1998

Journal of Cancer Research and Clinical Oncology

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Our study aimed to reveal whether the proliferation index of tumor cells, calculated with the monoclonal antibody (mAb) MIB1, is of prognostic relevance in patients with a gastric carcinoma and shows any correlation to well-known clinicopathological factors (TNM categories, stage, grade, Laurén type). We examined formalin-fixed, paraffin-embedded tissue blocks of samples from 94 patients, who underwent surgery for an adenocarcinoma of the stomach between 1988 and 1991. Specimens were immunohistochemically stained using the mAb MIB1 in combination with the alkaline-phosphatase/anti-(alkaline phosphatase) technique. The proliferation index (PI) was estimated in various areas of interest (tumor center and periphery and in lymph node metastases of compartments I and II), by always counting 200 tumor cells in three different high-power fields per specimen, and calculated as the percentage of MIB1-positive tumor cell nuclei relative to all tumor cell nuclei in the area examined. The total PI in the primary tumor was 47.2% and slightly higher in the center (49.1%) compared to the periphery (44.7%). Surprisingly in lymph node metastases the PI was lower than in the primary tumor (compartment I: 39.5%, compartment II: 33.6%). Tumors with distant metastases revealed a higher proliferative activity (55.1%) than tumors without (44.3%). The PI increased significantly from well to poorly differentiated carcinomas (P < 0.01), whereas the intestinal Laurén type showed a lower PI than the diffuse type. No difference in survival was found between patients with a median PI or less and those with a PI above the median (47.2%). Our results show that the proliferation index in gastric carcinomas has no prognostic relevance and therefore is of low clinical value.

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Gastric cancer heterogeneity

Cited by 39 publications

References 23 publications

Prognostic value of DNA flow cytometry in stomach cancer: a 5-year prospective study

Prognostic value of DNA flow cytometry in stomach cancer: a 5-year prospective study

Evaluating tumor heterogeneity in immunohistochemistry-stained breast cancer tissue

Assessment of the proliferation index in gastric carcinomas with the monoclonal antibody MIB 1

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