Andrea Schlemmer

Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting.

Blood vessel invasion has been associated with poor outcome in colorectal cancer (CRC), whereas the prognostic impact of lymphatic invasion is less clear. The authors of this report evaluated venous and lymphatic invasion as potential prognostic indicators in patients with CRC focusing on lymph node‐negative patients and compared routine and review pathology diagnoses.

Tumor necrosis is a new promising prognostic factor in colorectal cancer

The prognostic significance of tumor necrosis in colorectal cancer is unclear. Our study aimed to analyze the prognostic value of tumor necrosis with respect to progression-free and cancer-specific survival and to relate findings to expression of proteins involved in the control of cancer cell death, such as p53 and bcl-2. A total of 381 colorectal cancer specimens were retrospectively reevaluated. The extent of tumor necrosis was semiquantitatively assessed and recorded as either absent, focal (≤10% of the tumor area), moderate (10%-30%), or extensive (≥30%). Expression of p53 and bcl-2 was assessed immunohistochemically and recorded as either positive (using a cutoff value of 10%) or negative. In addition, mismatch repair protein status was assessed by immunohistochemistry using antibodies directed against hMLH1, hMSH2, and hMSH6. Tumor necrosis was observed in 365 (96%) cases, with 180 (47%) tumors showing focal necrosis, 119 (31%) moderate necrosis, and 66 (17%) extensive necrosis, respectively. Extent of necrosis was significantly associated with high T classification (P < .001), high N classification (P = .005), high International Union Against Cancer stage (P < .001), poor tumor differentiation (P < .001), large tumor size (P < .001), and blood vessel invasion (P = .01). No association of tumor necrosis with expression of p53, bcl-2, and mismatch repair protein status was observed. Tumor necrosis proved to be an independent prognostic variable with respect to progression-free and cancer-specific survival. In conclusion, tumor necrosis showed significant impact on prognosis of colorectal cancer patients. Its presence is readily assessable in hematoxylin and eosin-stained sections and should therefore routinely be commented upon in the pathology report.

Value of tumor size as a prognostic variable in colorectal cancer: a critical reappraisal.

Objectives: Vertical tumor growth, reflected by T classification, represents the most important prognostic variable in colorectal cancer. Our study aimed to investigate the impact of tumor size, particularly the maximum tumor diameter, on outcome of affected patients. Methods: A total of 381 colorectal cancer specimens were re-evaluated. Tumor size and location were extracted from the medical history and were known for 359 patients (94%). Receiver-operator characteristic analysis was applied to identify the optimal (maximum of sum of sensitivity and specificity) cut-off values with respect to prognostic impact. Results: Median tumor size was 4.5 cm (range, 0.6–15). Tumor size exceeding 4.5 cm was observed in 159 patients (44%) and was associated with high T and N classification, UICC stage, and tumor grade. At median follow-up of 45 months (range, 0–180), 141 patients (40%) showed tumor progression. Although 4.5 cm was identified as the optimal cut-off value within the whole group of patients, receiver-operator characteristic analysis restricted to different parts of the large bowel determined 5 cm, 5.3 cm, 3.9 cm, and 3.4 cm as cut-off values with the strongest discriminatory capacity in colon, right-sided colon, left-sided colon, and rectum cancers, respectively. Applying these cut-off values, tumor size was significantly associated with progression-free and cancer-specific survival in univariate and multivariate analyses in colon, yet not in rectum cancers. Conclusions: Tumor size proved to be an independent prognostic parameter for patients with colorectal cancer. Optimal cut-off values vary among different parts of the large bowel. Whereas prognostic significance is strong within the colon, it appears to be of minor value within the rectum.

Renal cell carcinoma metastatic to the stomach: single‐centre experience and literature review

To investigate the incidence, clinical presentation and therapy of gastric metastases, an uncommon finding, in a large group of patients with renal cell carcinoma (RCC).

Mucinous differentiation in colorectal cancer – indicator of poor prognosis?

Langner C, Harbaum L, Pollheimer M J, Kornprat P, Lindtner R A, Schlemmer A, Vieth M & Rehak P 
(2012) Histopathology 60, 1060–1072

Keratin 7 expression in colorectal cancer--freak of nature or significant finding?

Harbaum L, Pollheimer M J, Kornprat P, Lindtner R A, Schlemmer A, Rehak P & Langner C 
(2011) Histopathology59, 225–234

Clinicopathological significance of prolactin receptor expression in colorectal carcinoma and corresponding metastases

The role of human prolactin and its receptor, the prolactin receptor, in colorectal cancer is largely unknown. Our study aimed to assess the prevalence of prolactin receptor expression, its association with clinicopathological variables, as well as its prognostic value, comparing results of primary tissues with those of corresponding metastases. In all, 373 primary colorectal cancer and 171 corresponding metastases were evaluated for prolactin receptor expression by immunohistochemistry using a tissue microarray technique. Immunoreactivity was semiquantitatively scored as either focal (<10% of tumor cells positive), moderate (10–50%), or extensive (>50%). Prolactin receptor expression was related to clinicopathological parameters as well as patient outcome. To substantiate our findings, prolactin receptor expression was additionally assessed in HT-29 and SW-480 colorectal cancer cell lines using western blot. Prolactin receptor expression was observed in 360 out of 373 (97%) primary tumors, with 21 (6%) cases showing focal, 55 (15%) moderate, and 284 (76%) extensive expression, respectively. Extensive prolactin receptor expression was significantly associated with tumor size (P=0.002) and grade (P<0.001) as well as histological subtype (P<0.001). Somer’s D coefficients for concordance of primary tumors with corresponding lymph node and distant metastases were D=0.719 (P<0.001) and D=0.535 (P=0.001), respectively. Extensive prolactin receptor expression was significantly associated with disease progression (P=0.03) and cancer-specific survival (P=0.04) in patients with high-grade cancers. In conclusion, prolactin receptor expression is common in colorectal cancer, with high concordance between primary tumors and corresponding metastases. In view of evolving targeted therapy concepts in colorectal cancer, widespread prolactin receptor expression may offer a therapeutic perspective in affected patients.

Is there a rationale to record lymphatic invasion in node-positive colorectal cancer?

This study aimed to evaluate the prognostic significance of lymphatic invasion in colorectal cancers that have already spread to regional lymph nodes. 168 patients with node-positive tumours (colon, n=98; rectum, n=70) were retrospectively evaluated. Lymphatic invasion was assessed on H&E stained slides and univariable and multivariable analyses were applied. Lymphatic invasion was detected in 95 (57%) cases and was significantly associated with tumour and node classification and tumour differentiation. Patients with tumours showing lymphatic invasion had decreased progression-free survival (p=0.025) and cancer-specific survival (p=0.082). Stratified by location, lymphatic invasion was significantly associated with decreased progression-free (p=0.010) and cancer-specific (p=0.023) survival in colon cancers, yet not in rectal cancers. Multivariable analysis proved T4 (HR 2.18, 95% CI 1.40 to 3.39; p<0.001) and N2 (HR 1.68, 95% CI 1.07 to 2.66; p=0.03) as independent predictors of progression-free survival and T4 (HR 1.90, 95% CI 1.17 to 3.07; p=0.009), N2 (HR 2.27, 95% CI 1.38 to 3.73; p=0.001) and poor tumour differentiation (HR 2.18, 95% CI 1.39 to 3.43; p<0.001) as independent predictors of cancer-specific survival, while for lymphatic invasion no influence on outcome was noted. In conclusion, only tumour and node classification, and tumour differentiation proved to be independent prognostic variables in node-positive colorectal cancer and merit special attention in clinical decision-making.