BackgroundColorectal metastasis of lobular carcinoma of the breast is a diagnostic challenge. It may macroscopically simulate primary colon cancer or inflammatory bowel disease. In some cases, the interval between the primary breast cancer and metastatic colorectal lesions is so long that the critical records for diagnosis including history might be lost or missed.Case presentationReported herein is a case of metastatic lobular carcinoma of the breast masquerading as a primary rectal cancer developed in a 62-year-old Japanese woman. The case initially presented as a circumferential rectal lesion, and information on the patient’s history of breast cancer was not noted. As the result of endoscopic biopsy, diagnosis of poorly differentiated rectal adenocarcinoma was made. The lesion was surgically resected after chemo-radiotherapy. Histopathological examination of the resected specimen with hematoxylin and eosin (HE) stain revealed a single-file arrangement of the tumor cells, reminiscent of lobular carcinoma of the breast. Immunohistochemical analysis revealed an immunophenotype consistent with lobular carcinoma of the breast. Because further review of the patient’s history revealed an occurrence of ‘poorly differentiated adenocarcinoma of the breast’, which she had experienced 24 years earlier, the final diagnosis of the lesion was made as rectal metastasis from lobular breast carcinoma.ConclusionsPoorly differentiated adenocarcinoma of the colorectum is rarer than that of the stomach. Linitis plastica-type cancer of the colorectum is also rarer than that of the stomach. A lesson from the present case is that before we conclude a linitis plastica-type cancer of poorly differentiated type as a primary colorectal cancer, it is critical to exclude a possibility of metastatic colorectal cancer.

Abstract. The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.

The base excision repair gene MUTYH encodes glycosylase which removes adenine residues mispaired with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHG). Biallelic germline mutations of the MUTYH gene are known to cause multiple colorectal adenomas including polyposis and cancer, mostly due to G:C➝T:A transversions in proto-oncogenes or tumor suppressor genes. The risk of colorectal cancer (CRC) in monoallelic mutation carriers of MUTYH is estimated to be higher in comparison with non-carriers. To investigate the possible role in sporadic CRC, we examined alterations of the MUTYH gene including somatic mutations and allelic loss in 101 cases of sporadic CRC, together with the KRAS mutation in some cases. MUTYH mutations in cancer DNA were detected in 3 cases, while mutations were also found in DNA samples from normal tissues, indicating that all were germline mutations. Allelic loss at the MUTYH locus was found in 10 of 51 (20.0%) CRC cases and KRAS mutations were found in 33 of the 101 (32.7%) samples. There was no significant difference in the rate of G:C➝T:A transversion in KRAS between cases with allelic loss (1 of 10, 10.0%) and without allelic loss (9 of 41, 22.0%). Investigation of quantitative allelic imbalance at SNP rs3219489 of MUTYH showed that CRC cases with C allele dominance (minor type corresponding to His) were more frequently detected with G:C➝T:A transversions than in those with G allele dominance (major type corresponding to Gln). In conclusion, somatic alterations of MUTYH in sporadic CRC were rare, similar to other DNA repair genes. However, it is possible that unknown mutations of regions not analyzed in this study and epigenetic changes of the promoter region of MUTYH may contribute to the disease.

Purpose: FR901464 (FR) is an antitumor agent that specifically binds to and inhibits the function of splicing factor 3B subunit 1 (SF3B1). Higher frequencies of SF3B1 gene mutations and their relevance to cancer progression have been shown in studies of hematological malignancies. We assessed the frequencies of SF3B1 gene mutations in colorectal cancer (CRC) and the correlation of SF3B1 mutations and FR sensitivity in CRC. Experimental Design: We measured FR sensitivity in CRC cell lines to establish FR-resistant clones and performed DNA sequencing of all 25 SF3B1 exons in nine CRC cell lines, FR-resistant clones, and 16 CRC patients. On the basis our results, we performed further DNA sequencing in 80 CRC patients. Results: The FR IC50 values in all CRC cell lines were < 1ng/ml. Six FR-resistant clones were established: three from DLD1, two from HCT116, and one from LoVo cells. The FR IC50 of the FR-resistant clones was > 500-fold greater than that of their parental cells, although the IC50 of oxaliplatin or 5-fuluorouracil were the same. We found nonsense mutations in exon 10 of DLD1 cells and no significant mutations in the other samples. All the FR-resistant clones had the missense mutations in codon 1073 of exon 22. We found no mutation in exons 10, 22, and 12-15, which were previously reported in hematological malignancies in 80 CRC patients. Conclusion: Our data indicated the usefulness of the SF3B1 inhibitor as a novel molecular targeted drug for CRC and the other malignancies without codon 1073 mutations. Citation Format: Tomoki Yamano, Hidenori Nakajima, Satoshi Tsuda, Shuji Kubo, Mie Hamanaka, Masayoshi Kobayashi, Daisuke Yamagishi, Takashi Kuno, Kiyoshi Tsukamoto, Astuko Tamamoto, Masafumi Noda, Nagahide Matsubara, Dave SB Hoon, Naohiro Tomita. Low frequencies of SF3B1 mutations indicate SF3B1 inhibitor as a novel moleculartargeted drug for colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4350. doi:10.1158/1538-7445.AM2013-4350

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