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Background: While substantial evidence indicates that Ki67, a marker of proliferation, is strongly associated with breast cancer outcomes, its clinical utility has been limited given concerns about scoring inter-rater reliability and appropriate cut points. Nonetheless, Ki67 has been used in multiple clinical trials and results from POETIC indicated that low baseline Ki67 (ie, 10% would improve its clinical validity. Citation Format: Veronica C. Shim, Robin J Baker, Wen Jing, Sally S Agersborg, Thomas K Lee, Wamda Goreal, Ninah Achacoso, Catherine Lee, Marvella Villasenor, Amy Lin, Malathy Kapali, Laurel A Habel. Ki67 assessment based on international Ki67 working group recommendations and correlation with 21-gene assay results in a large integrated health care system: We might not be there yet [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-10.

Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied.To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors.Retrospective cohort study.A large, diverse, community-based health care system.3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016.Diagnostic yield of different LS screening strategies.Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC.Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics.The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed.Kaiser Permanente Northern California Division of Research.

The immunotherapeutic treatment of cancers using antibodies (naked or conjugated to a drug, toxin, or radionuclide) relies upon the preferential expression of a targeted antigen on the cancer cell compared to normal tissues. Polyclonal antiferritin antisera have shown selective distribution and therapeutic efficacy when radiolabeled in Hodgkin's disease and hepatoma. In this immunohistochemical study, we investigated the distribution of ferritin in tumors from 6 patients with Kaposi's sarcoma, 12 patients with Hodkgin's disease, and 9 patients with hepatoma, as well as in selected normal tissues. We found that the monoclonal antiferritin antibody binds primarily to histiocytes in samples from Kaposi's sarcoma and Hodgkin's disease. One hepatocellular carcinoma showed diffuse cytoplasmic staining with ferritin. Deposition of the monoclonal antibody was not detectable in the remaining hepatocellular carcinoma samples.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.

To better understand the molecular basis for the hormone-responsive phenotype in breast cancer, we have used a human cDNA array to compare patterns of gene expression between breast carcinoma cell lines discordant for estrogen receptor (ER) expression. These experiments indicated abundant expression of the transcription factor GATA-3 in the ER-positive cell lines MCF7 and T-47D, with minimal or no expression in the ER-negative cells lines MDA-MB-231 and HBL-100. Northern blot analysis of a panel of human breast carcinoma cell lines demonstrated a correlation between ER and GATA-3 expression. Studies of MCF7 cells grown in the absence or presence beta-estradiol indicated that GATA-3 expression was not responsive to estradiol. Protein immunoprecipitation and gel shift analysis confirmed the presence of functional GATA-3 protein in MCF7 but not in HBL-100 nuclear extracts. A panel of 47 primary breast cancers was characterized for expression of ER and GATA-3 using immunoperoxidase assay. In primary tumors, a statistically significant correlation between ER and GATA-3 expression was established (p < 0.0001, chi2). Our results indicate that GATA-3, in association with ER, is likely to regulate genes critical to the hormone-responsive breast cancer phenotype.

Bezoars are food or fiber concretions of the alimentary tract, which infrequently cause intestinal obstruction. The authors describe a case of a 7-year-old child with pica in whom a synthetic fiber bezoar obstruction of the small intestine developed at the site of a previously stapled intestinal anastomosis.

An 81-year-old man with a 3-year history of dysphagia underwent endoscopic resection of a 1-cm-diameter distal esophageal mass. Examination revealed a submucosal neoplasm with a circumscribed growth pattern composed of tubules, cysts, and papillae in association with a marked interstitial lymphoid infiltrate. The cyst lumens and papillae were lined by two to six layers of cytologically bland cuboidal to columnar cells with rare mitotic figures. The basal layer of cells was uniformly positive for smooth-muscle actin. Mucin-positive intracytoplasmic lumens were focally present, but cytoplasmic mucin was not seen. There was no evidence of Barrett's metaplastic epithelium. These features are similar to those in two, possibly three, previously reported cases of esophageal adenomas and bear a resemblance to sialadenoma papilliferum, a rare neoplasm of the minor salivary glands. Their clinicopathologic and immunohistologic features suggest that these neoplasms derive from the submucosal gland ducts. Comparison with the previously reported cases indicates that although the proportions of the various components (tubules, cysts, and papillae) may vary, all cases appear to pursue a slowly growing, clinically indolent course with no evidence of recurrence after complete resection.